Recent developments in the fungal transformation of steroids

REVIEW ARTICLE

Recent developments in the fungal transformation of steroids

NASSER NASSIRI-KOOPAEI & MOHAMMAD ALI FARAMARZI

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract Steroids constitute a vital part of the active ingredients in pharmaceuticals and intermediates used to produce medicines, and their application in chemical and agrochemical fi elds is also valued. The complex stereochemistry of steroids requires attention to regio- and stereoselectivity of the reaction during preparation, and therefore, biocatalytic methods are appro-priate for their production. This work reviews the recent application of fungi for the transformation of different steroid substrates, new biotransformation techniques, recently characterized reactions, and practical aspects, covering the period from 1990 to 2014. The future prospects of fungal biotechnology and biotransformation in the biopharmaceutical indus-try are also considered.

Keywords: Biotransformation , steroid , bioconversion , biocatalysis , fungus

Correspondence: Mohammad Ali Faramarzi, Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences Tehran, Iran. Tel: � 98-21-66954712. Fax: � 98-21-66954712. E-mail: [email protected]

(Received 16 January 2014 ; revised 18 April 2014 ; accepted 20 February 2015 )

Introduction

Steroids are a remarkable class of chemical com-pounds found throughout the animal and plant king-doms; this class includes sterols, such as cholesterol and ergosterol, bile acids, and a number of steroid hormones (Wang et al. 2002; Faramarzi et al. 2008a; Holland 2008). Modern scientifi c research on steroid chemistry and biochemistry began in the early 20th century. Research efforts in this fi eld were stimulated in the 1950s, with the discovery of the pharmaco-logical effects of cortisol and progesterone, two endogenous steroids, and with the identifi cation of the 11 α -hydroxylation activity of a Rhizopus species, a critical step in the development of the practical synthesis of biologically useful steroids. Growing numbers of microbial biotransformations of steroid compounds have been reported (Schmauder et al. 1991; Kardinahl et al. 2006; Whittall & Sutton 2010; Bhatti and Khera 2012; Donova and Egorova 2012), with an emphasis mainly on steroid hydroxylation, Δ 1 -dehydrogenation, and sterol side-chain cleavage. Many of these biotransformation reactions, in combination with chemical synthesis, have enabled researchers and industrialists to produce large quantities of steroid compounds (Liu et al. 2006;

Wuts et al. 2008; Dewick 2009; Faramarzi & Sadighi 2013). Whole-cell biotransformation reduces the production cost of steroids as it removes the need for isolation, purifi cation, and stabilization of pure enzymes (Bortolini et al. 1997; Riva 2001). Whole-cell biocatalysts also facilitate cofactor regeneration and concurrent reactions in a single fermentation cycle. The stereochemical aspects of biotransforma-tions are also attractive, since these enzymes can be good tools for selective chemical reactions (Bisogno et al. 2007).

Biotransformation-derived steroids are used for a wide range of pharmacotherapeutic purposes, such as anti-infl ammatory, immunosuppressive, proges-tational, diuretic, anabolic, and as neurosteroids, and also as contraceptive agents (Shahidi 2001; Brueggemeier et al. 2003). Researchers continue to discover more useful steroid compounds and also to isolate microorganisms that can perform the struc-tural transformations desired. The steroid biotrans-formation pathways of fungi are currently being developed through the use of genetic engineering techniques to manipulate metabolic pathways. In addition, knowledge on steroid transport phenomena across membranes is being expanded. Fermentation

Biocatalysis and Biotransformation, 2015; 33: 1–28

ISSN 1024-2422 print/ISSN 1029-2446 online © 2015 Informa UK, Ltd.DOI: 10.3109/10242422.2015.1022533

2 N. Nassiri-Koopaei & M. A. Faramarzi

media engineering, better lipophilic substrate solubi-lization, fungal immobilization, downstream process advancement, and design of continuous fermentation processes are of interest at the process design level (Kardinahl et al. 2006). Mahato and colleagues comprehensively described biotransformation reac-tions before 1990 (Mahato and Mukherjee 1984; Mahato and Banerjee 1985; Mahato et al. 1989); in this paper, fungal biotransformation reactions inves-tigated from 1990 to date are reviewed.

Chemistry and structure

Steroid molecules possess a common chemical skeleton of four fused rings consisting of three six-membered rings and a fi ve-membered ring. This hydrocarbon scaffold is a cyclopentanoperhydro-phenanthrene, which incorporates the three rings of phenanthrene (rings A, B, and C) and the cyclopen-tane ring (ring D) (Figure 1). The most common steroids and some of the major sites of biotransfor-mation reactions are depicted in Figures 2 and 3, respectively. Research on the microbial transforma-tion of steroids intensifi ed after World War II, when the anti-infl ammatory property of cortisone was discovered. Effi cient synthesis of corticosteroids was then required for scaling-up synthesis as well as structure-activity relationship studies. One of the particularly challenging conversions was the trans-position of the 12 α -hydroxy group in bile acid to C 11 , which required a 12-step reaction. In 1952, Peterson and Murray from Upjohn (Vasic-Racki 2006) reported the fi rst patented process of direct 11 α -hydroxylation of progesterone through the use of Rhizopus arrhizus and Rhizopus nigricans . One

unique feature of research on steroid chemistry has been the equivalent contribution to the fi eld from both academia and the pharmaceutical industry.

Chemical synthesis vs preparation through biotransformation

Chemical conversions may compromise the struc-tural integrity of the steroid, as many reagents may degrade one or more of the rings. Protection and deprotection are often needed to achieve the required regiochemical and stereochemical outcomes, while biotransformation processes need neither protection nor the use of hazardous reagents, and are therefore safer for working staff and the environment. Mild reaction conditions, and selective and specifi c reac-tions are key features of the biotransformation pro-cess, where11 α -hydroxylation activity by Rhizopus species, ring A aromatization, side-chain cleavage, and isomerization are classic fungal reactions. However, in most cases, a combination of chemical transformation and biotransformation is chosen (Mahato and Mukherjee 1984; Burger and Wolff 1997; Fernandes et al. 2003; Silva et al. 2011; Bhatti and Khera 2012).

Methods for biotransformation of steroids

Biotransformation in aqueous media and biotransformation facilitators

The major limitations on fungal steroid transforma-tion are low water solubility, dispersibility, and powder aggregation (Goetschel and Bar 1992). Increasing the permeability of viable cells has been considered as a remedy using substrate micronization, fed-batch systems, permeabilizing the cell wall using antibiot-ics, surfactants, or cyclodextrins by forming inclu-sion complexes, and organic solvents (Ni and Chen 2004). Compounds such as vancomycin, glycine, protamine, polymyxin B, nonapeptide, ethambutol, bacitracin, polyethyleneimine (PEI) (Malaviya and Gomes 2008), Tween (Smith et al. 1989), Triton X-110 and X-114 (Wang et al. 2004a; Wang et al. 2004b; Wang et al. 2005), and lecithin (Wang et al. 2002) have been assessed in this regard. These substances transfer steroids across the cell wall.

Biotransformation using immobilized biocatalysts

Whole-cell immobilization has been widely applied in fungal biotransformation of steroids to minimize loss of enzyme activity and maintain longer half-life (Ahmad et al. 1992; Mahato and Garai 1997; Fernandes et al. 2003; Quezada et al. 2008;

R1

R2R3

CyclopentanoperhydrophenanthreneCholestane (C27): R1= R2= CH3, R3= CH(CH3)(CH2)3CH(CH3)2

Pregnane (C21): R1= R2= CH3, R3= CH2CH3

Androstane (C19): R1= R2= CH3, R3= HEstrane (C18): R1: H, R2: CH3, R3: HGonane (C17): R1= R2= R3= H

A B

C D1

2

3

45

6

7

8

910

11

1213

1415

16

17

Figure 1. Basic steroid structure and structures of steroid stem names.

Fungal transformation of steroids 3

Carballeira et al. 2009). Viable immobilized cells provide advantages over conventional fermentation methods, including high volumetric reaction rates, high biomass retention in the reactor in continuous

processes, convenient downstream processing, enhanced operational and storage stabilities, reus-ability of immobilized biocatalysts, and increase in product yield (Junter and Jouenne 2004; Adrangi & Faramarzi 2013; Ghasemi et al. 2013; Mogharabi & Faramarzi 2014). Different immobilization tech-niques have been employed for whole-cell steroid biotransformation by bacteria and algae (Arabi et al. 2010; Saab et al. 2010). These include entrapment, adhesion to solid carrier surfaces, and micro-encapsulation. Synthetic polymers such as polyure-thane foams, photo-crosslinked resins, silicon-based polymers, and calcium-alginate beads (Ca-alginate) coated with a polyurea layer have been exploited (Leon et al. 1998). Kulkarni et al. (1998) immobilized Aspergillus niger NCIM 589 spores on high-density polyethylene (HDPE), using PEI for 11 α -hydroxylation of progesterone. Manosroi et al. (2008) studied the

HO

O

HO

OH

O

OH

O

O

O

OH

HO

OH

Cholesterol

Cortisol Progesterone

Testosterone Estradiol

Figure 2. Chemical structures of common steroids.

O

O

3-Reduction

6α/β-Hydroxylation




12α/β-Hydroxylation9α/β-Hydroxylation


1,2-DehyrdogenationSide chain cleavage

20-Reduction


Δ4,5-Reduction

Figure 3. Major sites of biotransformation reactions.


enhanced production of 17 α -hydroxyprogesterone from progesterone using the hydroxypropyl- β -cyclodextrin complexation technique by biotrans-formation with Curvularia lunata ATCC 12017. Houng et al. (1994) developed a novel technique of cell immobilization for increasing substrate partition to the gel matrix, by coating a thin layer of polyurea on the surface of Ca-alginate beads for bioconver-sion of progesterone to 11 α -hydroxyprogesterone by Aspergillus ochraceus, which was used by Chen et al. (1994). Peart et al. (2012) compared the transforma-tion reactions on 3 β ,17 β -dihydroxyandrost-5-ene using different free fungal cells with those carried out by macerated mycelia immobilized in Ca-alginate beads, and concluded that the latter method out-performed the traditional biotransformation. Wang et al. (1998) produced hydrocortisone from cortexolone-21-acetate using 11 β -hydroxylase from Absidia orchidis entrapped in Ca-alginate gel in a cosolvent-containing media, to increase the yield. They concluded that the process had better yield and could be applied in industry. Schlosser et al. (1993) studied the use of the free and Ca-alginate-immobilized Penicillium raistrickii i 477 cells for 15 α -hydroxylation of 13-ethyl-gon-4-en-3,17-dione. They also applied β -cyclodextrin, which increased the lipophilic sub-strate solubility and availability.

Biotransformations using free and immobilized enzymes

Some efforts have been devoted to isolate and char-acterize enzymes from fungal sources for industrial and research purposes (Petri č et al. 2010). Biotrans-formation enzymes can be regarded as suitable substitutes for production of active pharmaceutical ingredients, as they have a lower cost, are less time consuming and more environmentally friendly, while also being selective (Manosroi et al. 2007).

Enzymes are classifi ed into six classes, some of which are essential in biocatalytic processes. These classes include oxidoreductases, transferases, hydro-lases, lyases, isomerases, and ligases (Faber 2011). The main enzymatic classes underlying biotransfor-mation reactions in certain fungi are presented below.

Hydroxylases . Hydroxylases insert a hydroxyl group at a specifi c carbon atom of a steroid compound. They carry out the most prevalent class of fungal steroid biotransformation reactions (Bhosale et al. 2006). Fungal hydroxylation can introduce OH groups in a cost effective and reliable way, especially for adrenocortical hormone production (Holland 1999; Ni and Chen 2004; Borges et al. 2009). Dif-ferent fungi are capable of uniquely hydroxylating almost every carbon atom in the steroidal structure

(1 β , 2 β , 4 {on aromatic ring}, 5 α , 6 β , 7 α , 7 β , 9 α , 10 β , 12 α , 12 β , 14, 15 α , 15 β , 17 α , 19, 22, and 26), with 11 α , 11 β , and 16 α -hydroxylases providing the most commercial value (Faramarzi et al. 2003; Fer-nandes et al. 2003; El-Kadi and Mostafa 2004; Chen et al. 2007; Faramarzi et al. 2007; Yang et al. 2007; Faramarzi et al. 2008c; Kalbasi et al. 2009; Peart et al. 2011) (Scheme 1).

5 a -Reductases . Reductases, also known as 3-oxo-5 α -steroid 4-dehydrogenases, reduce the double bond in steroids such as androgens, estrogens, and bile acids. Penicillium spp. (for example, Penicillium decumbens , Penicillium chrysogenum , and Penicillium crustosum ) (Murray 2000; Cabeza et al. 1999) are some of the most well-established producers of this enzyme.

3 b -Hydroxysteroid dehydrogenases/ Δ 5 - Δ 4 -isomerases . The 3 β -hydroxysteroid dehydrogenase/ Δ 5 - Δ 4 isomerase (3 β -HSD) isoenzymes are responsible for the oxida-tion and isomerization of Δ 5 -3 β -hydroxysteroid pre-cursors into Δ 4 - ketosteroids, catalyzing an essential step in the formation of all classes of active steroid hormones (Simard et al. 2005; Hunter et al. 2009).

17 b -Hydroxysteroid dehydrogenases . 17 β -Hydroxys-teroid dehydrogenases (17 β -HSD) are pivotal in controlling the biological potency of steroid hor-mones by catalyzing oxidation or reduction at C 17 . 17 β -HSDs may also metabolize other substrates like alcohols, bile acids, fatty acids, and retinols (Adamski and Jakob 2001). A number of different fungi such as Candida tropicalis , Cryptococcus tsukubaensis , Saccharomyces cerevisiae , Hortaea werneckii , Trimato-stroma salinum , Cylindrocarpon radicicola , Cochliobolus lunatus , and Pleurotus ostreatus have been shown to produce 17 β -HSD (Itagaki and Iwaya 1988; Ri ž ner et al. 1996; Ri ž ner et al. 2001; Mindnich et al. 2004; Donova et al. 2005).

Steroid C-1/C-2 dehydrogenases . Steroid C-1/C-2 dehydrogenases are not so prevalent in fungi but Nectria haematococca ( Fusarium solani ) is regarded as an exception that is able to produce this enzyme and shows substrate specifi city (Ahmed et al. 1996).

C-17 – C-20 Lyase . C17 � C20 Lyase (C17, 20-lyase) is one of the key enzymes that are responsible for the biosynthesis of androgens in N. haematococca (Ahmed et al. 1996).

Oxidoreductases . Laccase is a widely known oxidase that catalyzes the reduction of ketones to alcohols. The enzyme has been used to remove estrogenic compounds from environmental samples (Tamagawa


et al. 2006; Ma et al. 2007; Lloret et al. 2010; Aghaie-Khouzani et al. 2012; Mogharabi et al. 2012; Ueda et al. 2012) (Schemes 2 and 3).

Some steroid-metabolizing enzymes, in particu-lar those of industrial importance, have been expressed in heterologous hosts (Kristan et al. 2007). 17 β -HSD has been expressed in recombinant E. coli allowing the whole cells or purifi ed enzyme to be used for specifi c reduction of 17-ketosteroids (for example, synthesis of androgenic anabolic molecules). Saccharomyces cerevisiae was also used to express a mammalian hydroxylase for stereospecifi c hydroxylation of dehydroepiandrosterone by Vico

et al. (2002). Modifying the specifi city of fungal steroid-transforming enzymes by site-directed muta-genesis is also proving to be an interesting approach.

New techniques for selective transformations

Fungal spores have been used to transform steroids, including 11 α -hydroxylation and 11 β -hydroxylation reactions with Aspergillus ohcraceus and Stachylidium theobromae , respectively (Wolken et al. 2003). Their ability to endure harsh conditions and toxic compounds makes using spores a practical alterna-tive to conventional microorganisms (Wolken et al.

O

OH

17α-Ethyl-19-nortestosterone 15α-Hydroxy-17α-ethyl-19-nortestosterone

CH3CH3

O

OHCH3CH3

OH

Fusarium culmorum

120 rpm, 3 days, 20 °C

O

O

OH

Rhizopus stolonifer

120 rpm, 10 days, 28 °C O

OH

OH

Oxandrolone 9α-Hydroxyoxandrolone

Acremonium strictum

150 rpm, 6 days, 25 °C O

OH

17α-Methyltestosterone

HO

OH

3,17β-Dihydroxy-17β-methylestra-1,3,5(10)-triene

OH

O

OH6β,17β-Dihydroxy-17β-methylandrosta-1,4-dien-3-one

OH

O

O

OH

Corynespora cassiicola

120 rpm, 5days, 30 °C

OH

O

O

OH

OH

Cortexolone 8β,17α-21-Trihydroxypregn-4-en-3,20-dione

+

Scheme 1. Hydroxylation reactions.


2003). Lu et al. (2006) studied the effect of two-stage addition of the substrate cortexolone-21-ace-tate on the expression of cytochrome P450 and the production of hydrocortisone by Curvularia lunata CL-114. They concluded that this strategy was much better than the original one due to the improved induction of cytochrome P450 and therefore the yield of hydrocortisone. Fungi like yeasts have been investigated as development tools for the merger of biology and synthesis to produce targeted secondary metabolites that can introduce new applications (Siddiqui et al. 2012; Lu et al. 2013).

Biotransformation in two-phase systems

Aqueous organic two-phase systems are often applied to improve the yield of fermentations in which lipo-philic substrates and products are present (Leon et al. 1998; Cruz et al. 2001; Cruz et al. 2002; Faramarzi et al. 2008c; Arabi et al. 2009). Both substrate and product are contained in a water-immiscible organic phase, keeping the substrate concentration in the aqueous phase at a constant value and extracting the metabolic products, enabling simple recovery of product. Organic solvents should be non-toxic to the fungus and provide adequate partition and mass

transfer characteristics (Leon et al. 1998; Collins and Daugulis 1999; Wang and Dai 2010; Wu et al. 2011). Two-phase systems have been applied in biotransformations by bacteria and microalgae, but limited studies have been published regarding their application in fungal biotransformation (Nikolova and Ward 1992; Carvalho et al. 2009; Marques et al. 2010). Santhanam and Shreve (1994) studied the bioconversion of cortexolone by Curvularia lunata to examine the effects of solvents on multiphase bioconversion reactions. Recently, environmental concerns have prompted researchers to design new solvent systems to replace traditional organic sol-vents, which could jeopardize human health and ecosystems. In this regard, one breakthrough is the application of super critical fl uid technology in biotransformation reactions (Carvalho et al. 2009; Brandenbusch and Sadowski 2010).

Biotransformation in a cloud point system

Cloud point systems (CPS) prepared by using non-ionic surfactants, provide a micro-aqueous environ-ment to ensure the viability of cells and their enzymatic activity. Water vesicles containing the bio-catalyst are homogeneously dispersed in the surfac-

O

OH

Testosterone

O

O

OH

Chaetomium sp.

120 rpm, 9 days, 25 °C

O

HO

Penicillium lilacinum

150 rpm, 3 days, 25 °C O

O

ProgesteronePregnenolone

O

OH

19-Nortotestosterone

Absidia glauca

120 rpm, 3-7 days, 27 °C O

OH

19-Norandrostenedione

7β-Hydroxytestosterone

Scheme 2. Oxidation reactions.


tant-rich continuous phase. Therefore, toxicity, substrate inhibition, and the organic phase are sig-nifi cantly reduced. The biotransformation occurs within water vesicles containing the biocatalysts, and the product is extracted back into the continuous phase, protecting it from degradation (Wang et al. 2004a; Wang et al. 2005; Wang et al. 2008). Wang et al. (2004b) studied the transformation of choles-terol to androst-1,4-diene-3,17-dione and androst-4-ene-3,17-dione in a cloud point system, using Mycobacterium spp. NRRL B 3683. Limited studies are available on fungal biotransformation in cloud point systems.

Microemulsions and liposomes as alternative biotransformation systems

Loss of cell viability and low interfacial mass transfer area can limit biotransformations in organic media. Microemulsions signifi cantly increase the interfacial area mass transfer compared to biphasic systems. However, long exposure to the organic solvent in microemulsions decreases the bioactivity of the cells, resulting in lower productivity. Such adverse side effects can be solved, to some extent, using lipo-somes. Hence, liposomal media provide a good

alternative for performing steroid biotransformation with high productivity (Stefan et al. 2002).

Biotransformations performed on different sub-strates by fungal species and categorized based on their chemical reactions are depicted in Table I.

Commercial benefi t of therapeutic steroids produced by biotransformation

Steroids are widely used pharmaceuticals, and fun-gal hydroxylases and oxidoreductases have been used in their production, particularly in the production of anti-infl ammatory substances, e.g., 11 α -hydroxylase, 11 β -hydroxylase, and 5 α -reductase (Hu et al. 1995; Boynton et al. 1997; Cotillon and Morfi n 1999; Dray and Cotillon 1999). These enzymes can be used for the production of bile acids (7 α -hydroxylase), neurosteroids (5 α -reductase), cardioactive steroids (14 α -hydroxylase), androgens (3 β -HSD, 17 β -HSD, 5 α -reductase, Δ 1 -dehydrogenase, etc.), and progestins ( Δ 1 -dehydrogenase, 11 α -hydroxylase, 11 β -hydroxylase, etc.) (Vitas et al. 1997; Yazdi and Hosseini 2002; Fernandes et al. 2003; Burton 2003; Faramarzi et al. 2004; Yazdi et al. 2005; Faramarzi et al. 2009; Zhang et al. 2011; Wang et al. 2013a; Zhang et al. 2013b).

o

o

Androst-4-en-3,17-dione

o

OH

17β-Hydroxyandrost-1,4-dien-3-one

Acremonium strictum

120 rpm, 6 days, 27 °C

HO

o

Dehydroepiandrosterone

Penicillium glabrum

130 rpm, 24 hHO

O O

3β-Hydroxy-17α-oxa-D-homo-5α-androstan-17-one

O

OO

Adrenosterone

Cunninghamella elegans

120 rpm, 72 h, 26 °C O

OOH

11-Ketotestosterone

Scheme 3. Reduction reactions.


Tab

le I

. F

unga

l tr

ansf

orm

atio

ns o

f st

eroi

ds.

Sub

stra

teM

icro

orga

nism

Pro

duct

Met

hod

of

Bio

tran

sfor

mat

ion

Yie

ld %

Ref

eren

ce

Hyd

roxy

latio

n A

ndro

st-1

,4-d

ien-

3,17

-dio

ne A

crem

oniu

m s

tric

tum

15

α -H

ydro

xyan

dros

t-1,

4-di

en-3

,17-

dion

eW

hole

-cel

l, S

haki

ng fl

ask

6.2

Far

amar

zi e

t al

. 20

06

15 α -

Hyd

roxy

andr

ost-

4-en

-3,1

7-di

one

1915

α ,17

β -D

ihyd

roxy

andr

ost-

1,4-

dien

-3-o

ne4.

53 β

-Hyd

roxy

andr

ost-

5-en

-17-

one

(DH

EA

) G

ibbe

rella

zea

e V

KM

F

-260

03 β

,7 α -

Dih

ydrd

oxy-

andr

ost-

5-en

-17-

one

Who

le-c

ell,

Sha

king

fl a

sk71

.2L

obas

tova

et

al.

2009

Epi

andr

oste

rone

Bea

uver

ia b

assi

ana

3 β ,1

1 α -D

ihyd

roxy

-5 α -

andr

osta

n-17

-one

3 β ,1

1 α ,1

7 β -T

rihy

drox

y-5 α

-and

rost

ane

3 β ,1

1 α -D

ihyd

roxy

-17 α

-oxa

-D-h

omo-

5 α -a

ndro

stan

-17-

one

Who

le-

cell,

S

haki

ng fl

ask

7 8 9

Ś wiz

dor

et a

l. 20

11

DH

EA

11 α -

Hyd

roxy

-DH

EA

3 β ,1

1 α ,1

7 β -T

rihy

drox

yand

rost

-5-e

ne 3 β

,11 α

-Dih

ydro

xy-1

7 α -o

xa-D

-hom

o-an

dros

t-5-

en-1

7-on

e

10 11 12A

ndro

sten

edio

l3 β

,12 α

,17 β

-Tri

hydr

oxya

ndro

st-5

-ene

3 β ,1

2 α -D

ihyd

roxy

-17 α

-oxa

-D-h

omo-

andr

ost-

5-en

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one

11 12A

ndro

sten

edio

ne11

α -H

ydro

xyan

dros

t-4-

en-3

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dion

e

11 α -

Hyd

roxy

test

oste

rone

11 α -

Hyd

roxy

-17 α

-oxa

-D-h

omo-

andr

ost-

4-en

-3,1

7-di

on

13 14 15P

roge

ster

one

11 α -

Hyd

roxy

prog

este

rone

6 β ,1

1 α -D

ihyd

roxy

prog

este

rone

11 α -

Hyd

roxy

test

oste

rone

11 α ,

17 β -

Dih

ydro

xy-5

β -an

dros

tan-

3-on

e

16 17 14 18A

ndro

sten

edio

ne C

haet

omiu

m s

p. K

CH

66

5114

α -H

ydro

xyan

dros

t-4-

en-3

,17-

dion

eW

hole

-cel

l, S

haki

ng fl

ask

75Ja

necz

ko e

t al

. 20

09

3 β -H

ydro

xy-5

α -an

dros

tan-

17-o

ne C

epha

losp

oriu

m

aphi

dico

la

3 β ,1

2 α ,1

7 β -t

rihy

drox

y-5 α

-and

rost

ane

3 β ,1

4 α -D

ihyd

roxy

-5 α -

andr

osta

n-17

-one

3 β ,5

α -D

ihyd

roxy

-5 α -

andr

osta

n-17

-one

Who

le-c

ell,

Sha

king

fl a

sk12 2 4

Ben

sass

on e

t al

. 19

98

3 β -H

ydro

xyan

dros

t-5-

en-1

7-on

e3 β

,7 α -

Dih

ydro

xyan

dros

t-5-

en-1

7-on

e

3 β ,7

β -D

ihyd

roxy

andr

ost-

5-en

-17-

one

3 β ,1

1 α -D

ihyd

roxy

andr

ost-

5-en

-17-

one

3 β ,5

α ,6 β

-Tri

hydr

oxya

ndro

stan

-17-

one

25 31 6 63 β

,19-

Dih

ydro

xyan

dros

t-5-

en-1

7-on

e3 β

,5 α ,

6 β ,1

9-T

etra

hydr

oxya

ndro

stan

-17-

one

84 β

,17 β

-Dih

ydro

xy-4

α -m

ethy

l-5 α

-an

dros

tane

Cep

halo

spor

ium

ap

hidi

cola

4 β

,7 α -

Dih

ydro

xy-4

α -m

ethy

l-5 α

-and

rost

an-1

7-on

e 4 β

,15 α

,17 β

-Tri

hydr

oxy-

4 α -m

ethy

l-5 α

-and

rost

ane

Who

le-c

ell,

Sha

king

fl a

sk10 7

Ben

sass

on e

t al

. 19

99

4 β ,1

7 β -D

ihyd

roxy

-4 α ,

17 α -

dim

ethy

l-5 α

-an

dros

tane

4 β ,7

α ,17

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et

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gest

eron

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ham

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le I

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onti

nued

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Who

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sk10 24

Hun

ter

et a

l. 20

08

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rost

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ium

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Who

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ell,

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king

fl a

sk37 10

Ben

sass

on e

t al

. 19

99

19-N

orte

stos

tero

ne C

epha

losp

oriu

m

aphi

dico

la

19-N

oran

dros

t-4-

en-3

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dion

eW

hole

-cel

l, S

haki

ng fl

ask

1H

anso

n et

al.

1996

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rost

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n-3,

17-d

ione

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rosp

ora

cras

sa

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roxy

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Who

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ell,

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king

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sk21

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25.7

15.3 8.7

9.8

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amar

zi e

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. 20

08

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drol

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deca

noat

e A

crem

oniu

m s

tric

tum

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15 α -

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Who

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di e

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06

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ctor

um

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CC

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roxy

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ost-

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hole

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l, S

haki

ng fl

ask

ND

Che

n et

al.

2010

Deh

ydro

epia

ndro

ster

one

(DH

EA

) Pe

nici

llium

gr

iseo

purp

ureu

m

Sm

ith

and

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cilli

um

glab

rum

(W

ehm

er)

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tlin

g

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rost

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ell,

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king

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sk11

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ng e

t al

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10

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tero

ne F

usar

ium

cul

mor

um

6 β -H

ydro

xy-1

9-no

rand

rost

ened

ione

Who

le-c

ell,

Sha

king

fl a

sk48

Ś wiz

dor

2005

4-M

ethy

ltes

tost

eron

e6 β

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roxy

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ethy

land

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ened

ione

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ster

one

Cha

etom

ium

sp.

KC

H

6651

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ydro

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dros

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dion

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hole

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l, S

haki

ng fl

ask

21Ja

necz

ko e

t al

. 20

09

19-N

orte

stos

tero

ne Tr

icho

derm

a ha

mat

um

11 α -

Hyd

roxy

estr

-4-e

n-3,

17-d

ione

Est

r-1,

4-di

en-3

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dion

eW

hole

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l, S

haki

ng fl

ask

32 26B

artm

a ń sk

a 20

07

Tab

le I

. (C

onti

nued

)

Sub

stra

teM

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orga

nism

Pro

duct

Met

hod

of

Bio

tran

sfor

mat

ion

Yie

ld %

Ref

eren

ce


1-D

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rote

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tero

ne11

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l6 α

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one

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roxy

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one

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thyn

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tero

ne11

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en-3

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dion

e70

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obuf

agin

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or s

pino

sus

and

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ergi

llus

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acet

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nobu

fagi

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oxo-

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obuf

agin

Who

le-c

ell,

Sha

king

fl a

sk6.

2 4.

5H

e et

al.

2006

b

Tes

tost

eron

e pr

opio

nate

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cilli

um n

otat

um

15 α -

Hyd

roxy

andr

ost-

4-en

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one

Who

le-c

ell,

Sha

king

fl a

sk29

Bar

tma ń

ska

et a

l. 20

05

19-N

orte

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tero

ne A

bsid

ia g

lauc

a 19

-Nor

andr

oste

nedi

one

Who

le-c

ell,

Sha

king

fl a

sk21

Hus

zcza

200

3b

Pre

dnis

olon

e A

crem

oniu

m s

tric

tum

11

β -H

ydro

xyan

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dion

eW

hole

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l, S

haki

ng fl

ask

ND

Far

amar

zi e

t al

. 20

08d

Pre

gnen

olon

e Pe

nici

llium

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cinu

m

AM

111

DH

EA

Pro

gest

eron

e A

ndro

sten

edio

ne

Who

le-c

ell,

Sha

king

fl a

sk42 15

Ko ł

ek e

t al

. 20

08

Pro

gest

eron

e Pe

nici

llium

au

rant

iogr

iseu

m

And

rost

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n-3,

17-d

ione

Who

le-c

ell,

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king

fl a

skN

DG

hara

ei-F

atha

bad

and

Aro

ona

(201

1)P

hyto

ster

ol F

usar

ium

mon

ilifo

rme

And

rost

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n-3,

17-d

ione

Who

le-c

ell,

Sha

king

fl a

skH

igh

Lin

et

al.

2009

3 β -A

cety

lam

ino-

5 α -p

regn

an-2

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e R

hizo

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arrh

izus

3 β

-Ace

tyla

min

o-5 α

-pre

gnan

-12,

20-d

ione

Who

le-c

ell,

Sha

king

fl a

sk17

Hol

land

et

al.

1998

Pro

gest

eron

e N

ectr

ia h

aem

atoc

occa

A

ndro

sten

edio

neW

hole

-cel

l, S

haki

ng fl

ask

3.5

Ahm

ed e

t al

. 19

96

Tes

tost

eron

e ac

etat

e M

ycel

ioph

thor

a th

erm

ophi

la

And

rost

-4-e

n-3,

17-d

ione

Who

le-c

ell,

Sha

king

fl a

sk10

Hun

ter

et a

l. 20

09

Tes

tost

eron

eA

ndro

st-4

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3,17

-dio

ne8

Tes

tost

eron

e C

oryn

espo

ra c

assi

icol

a C

BS

161

.60

And

rost

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n-3,

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ione

Who

le-c

ell,

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king

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sk5

Hun

ter

et a

l. 20

11

Red

uctio

n A

ndro

st-1

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3,17

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ne A

crem

oniu

m s

tric

tum

17

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en-3

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tost

eron

e

Who

le-c

ell,

Sha

king

fl a

sk23

.3 4.5

0.92

Far

amar

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t al

. 20

06

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andr

oste

rone

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uver

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assi

ana

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1 α ,1

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rihy

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Who

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ell,

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king

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sk8

Ś wiz

dor

et a

l. 20

11

DH

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Who

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king

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sass

on e

t al

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98

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ost-

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drox

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rost

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ne6

(Con

tinue

d )


Deh

ydro

epia

ndro

ster

one

(DH

EA

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nici

llium

gr

iseo

purp

ureu

m

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ith

and

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cilli

um

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rum

(W

ehm

er)

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tlin

g

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ydro

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rost

an-1

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eW

hole

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l, S

haki

ng fl

ask

2H

uang

et

al.

2010

And

rost

ened

ione

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char

omyc

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erev

isia

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esto

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one

Who

le-c

ell,

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lode

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n m

ediu

m

faci

litat

or

ND

Sin

ger

et a

l. 19

91

19-N

orte

stos

tero

ne F

usar

ium

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mor

um

6 β -H

ydro

xy-1

9-no

rand

rost

ened

ione

Who

le-c

ell,

Sha

king

fl a

sk48

Ś wiz

dor

2005

19-N

oran

dros

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dion

e6 β

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ster

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154-

Met

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sten

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ne10

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otes

tost

eron

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ne 3 β

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22 39T

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ster

one

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cilli

um c

rust

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rone

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HT

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hole

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l, S

haki

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ask

ND

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res

et a

l. 20

03

And

rost

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ne S

chiz

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omyc

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tost

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hole

-cel

l, S

haki

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ask

ND

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ic e

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99

17 α ,

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roxy

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um v

ar.

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rihy

drox

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neW

hole

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l, S

haki

ng fl

ask

ND

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on e

t al

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99

And

rost

ened

ione

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cilli

um n

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um

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stan

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one

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tola

cton

eW

hole

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l, S

haki

ng fl

ask

9 82B

artm

a ń sk

a et

al.

2005

Hyd

roco

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one

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ium

str

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m

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CC

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211

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trih

ydro

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4-en

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neW

hole

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l, S

haki

ng fl

ask

11.2 7.6

Far

amar

zi e

t al

. 20

02

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enos

tero

ne C

unni

ngha

mel

la e

lega

ns

11-K

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esto

ster

one

9 α -H

ydro

xy-1

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tote

stos

tero

ne 6 β

-Hyd

roxy

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keto

test

oste

rone

Who

le-c

ell,

Sha

king

fl a

sk8.

7

12.4

13.8

Cho

udha

ry e

t al

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07

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xyco

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rone

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halo

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Who

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ell,

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king

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sk9.

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n 19

98

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l, S

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05

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rost

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ell,

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king

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sk10 4

Hun

ter

et a

l. 20

09

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poxy

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ne C

oryn

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161

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20®

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xy-1

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gn-4

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neW

hole

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l, S

haki

ng fl

ask

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unte

r et

al.

2011

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roco

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one

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ora

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sa

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etra

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le-c

ell,

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king

fl a

sk18

.75

Fat

haba

d et

al.

2006

Tab

le I

. (C

onti

nued

)

Sub

stra

teM

icro

orga

nism

Pro

duct

Met

hod

of

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tran

sfor

mat

ion

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ld %

Ref

eren

ce


Hyd

roly

sis

(Sch

eme

4)N

andr

olon

e de

cano

ate

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emon

ium

str

ictu

m

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r-4-

en-3

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dion

e

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roxy

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one

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roxy

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ione

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Dih

ydro

xyes

tr-4

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3-on

e

Who

le-c

ell,

Sha

king

fl a

sk20

.4

16.6 4.9

5.6

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di e

t al

. 20

06

Tes

tost

eron

e pr

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nate

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hode

rma

ham

atum

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ndro

st-1

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hole

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l, S

haki

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artm

a ń sk

a 20

07

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tost

eron

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nate

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cilli

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Who

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ell,

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king

fl a

sk61 29 9

Bar

tma ń

ska

et a

l. 20

05

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seno

side

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acch

ari

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c C

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hole

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l, S

haki

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ask

57.3

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Scheme 4. Hydrolysis reactions.

HO

Phytosterol

o

o

Fusarium moniliforme

150 rpm, 72 h, 30 °C

OH

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Neurospora crassa

120 rpm, 5 days, 25 °C O

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Hydrocortisone 11β-Hydroxyandrost-4-en-3,17-dione

Androst-4-en-3,17-dione

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OHO

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Acremonium strictum

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O

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Scheme 5. Side-chain degradations.


The products of methyl protodioscin bioconver-sion showed cytotoxicity in malignant cell culture (He et al. 2006a; Groussin and Antoniotti 2012), while Chen et al. (2010) studied the inhibitory effects of ruscogenin metabolites on tissue factor expression in the human monocyte cell line THP-1 cells stimulated by tumor necrosis factor-alpha (TNF- α ). Microbial steroid transformation might also be important in diagnostic medicine (Bredeh ö ft et al. 2012).

7 α -Hydroxylases are of biotechnological use in the production of bile acids for replacement therapy, dissolution of cholesterol gallstones, and as potential carriers of liver-specifi c drugs or absorption enhanc-ers (Forootanfar et al. 2011, Irrgang et al. 1997). 7 α -Hydroxylase activity can also be used for the production of immune modulators (Lobastova et al. 2009), while 11 β -hydroxylases are used in the production of anti-infl ammatory substances (Suzuki et al. 1993; Paraszkiewicz and D ł ugo ń ski 1998; Petri č et al. 2010). 14 α -Hydroxylases also show potential for pharmaceutical application.

Researchers have used microbial and fungal biotransformation reactions for the discovery of new compounds (Venisetty and Ciddi 2003; Ye et al. 2004; Liu and Yu 2010; Pervaiz et al. 2013). Steroid drugs, specifi cally, have been a particular focus as microbial biotransformations may mimic those of human metabolism (Tong and Dong 2009). These compounds can also be applied for therapeutic goals, especially for metabolic defi ciencies (Tin et al. 2011).

Č re š nar et al. (2009) have reviewed the toxicity of some mammalian steroid hormones to fungi, for prevention of fungal infections. Expanding our knowledge of steroid detoxifi cation through biotrans-formation can provide information on mechanisms of drug resistance in fungal infections. Dong et al. (2010) studied the pathways and kinetics of Dioscorea zingiberensis biotransformation by Aspergillus oryzae . Microbial transformation of dihydrotestosterone (DHT) by using Macrophomina phaseolina and Gibberella fujikuroi resulted in some potent butyryl-cholinesterase (BChE) inhibitors (Zafar et al. 2013).

Paraszkiewicz et al. (2002) investigated a bio-surfactant produced by the fungus Curvularia lunata and its possible role in the effi ciency of biotransformation. Ž nidar š i č et al. (1998) used the non-coagulative type of the pelleted form of the fi lamentous fungus Rhizopus nigricans to hydroxylate progesterone at the 11 α -position, and they investi-gated the parameters infl uencing the effi ciency of biotransformation.

Environmental applications

Steroid compounds are major environmental pollut-ants that can affect human health, with estrogens and anabolic steroids being prominent among them. These compounds may be biodegraded by microorganisms, which can lead to detoxifi cation, or potentially, an increase in toxicity. The characteriza-tion and defi nition of the processes involved would

O

O

O

Cinobufagin

O

O

O

HO

oO

O

O

HO

Mucor spinosus

180 rpm, 72 h, 28 °C

3-epi-12β-Hydroxyl cinobufagin

OH

Scheme 6. Isomerization.

OO

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OHO

O

HO

H

O

H

OH

H

H

O

OH

OH

Gliocladium deliquescens

180 rpm, 144h, 28 °C

Ruscogenin Glycosylated Ruscogenin

Scheme 7. Glycosylation.


assist with hazard removal (Lisowska and D ł ugonski 2003; McAdam et al. 2010; Silva et al. 2012).

Declaration of interest : The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

References

Adamski J , Jakob FJ . 2001 . A guide to 17 β -hydroxysteroid dehy-drogenases . Mol Cell Endocrinol 171 : 1 – 4 .

Adrangi S , Faramarzi MA . 2013 . From bacteria to human: a journey into the world of chitinases . Biotechnol Adv 31 : 1786 – 1795 .

Aghaie-Khouzani M , Forootanfar H , Moshfegh M , Khoshayand MR , Faramarzi MA . 2012 . Decolorization of some synthetic dyes using optimized culture broth of laccase producing ascomycete Paraconiothyrium variabile . Biochem Eng J 60 : 9 – 15 .

Ahmad S , Garg S , Johri B . 1992 . Biotransformation of sterols: selective cleavage of the side chain . Biotechnol Adv 10 : 1 – 67 .

Ahmed F , Williams RAD , Smith KE . 1996 . Microbial transforma-tions of steroids . X. Cytochromes P-450 11 α -hydroxylase and C17-C20 lyase and a 1-ene dehydrogenase transform steroids in Nectria haematocca . J Steroid Biochem Mol Biol 58 : 337 – 349 .

Al-Aboudi A , Mohammad MY , Musharraf SG , Choudhary MI , Atta-ur-Rahman . 2008 . Microbial transformation of testoster-one by Rhizopus stolonifer and Fusarium lini . Nat Prod Res 22 : 1498 – 1509 .

Arabi H , Yazdi MT , Faramarzi MA . 2009 . Application of organic mono-phase and organic - Aqueous two-liquid-phase systems in microalgal conversion of androst-4-en-3,17-dione by Nostoc muscorum . Biocatal Biotransform 27 : 219 – 225 .

Arabi H , Yazdi MT , Faramarzi MA . 2010 . Infl uence of whole microalgal cell immobilization and organic solvent on the bioconversion of androst-4-en-3,17-dione to testosterone by Nostoc muscorum . J Mol Catal B Enzym 62 : 213 – 217 .

Bartma ń ska A , Dmochowska-G ł adysz J . 2007 . Transformation of steroids by Trichodermahamatum . Enzyme Microb Technol 40 : 1615 – 1621 .

Bartma ń ska A , Dmochowska-G ł adysz J , Huszcza E . 2005 . Steroids ’ transformations in Penicillium notatum culture . Steroids 70 : 193 – 198 .

Bensasson CM , Hanson JR , Hunter AC . 1998 . The hydroxylation of Δ 5 -androstenes by Cephalosporium aphidicola . Phytochemis-try 49 : 2355 – 2358 .

Bensasson CS , Chevolot Y , Hanson JR , Quinton J . 1999 . The microbiological hydroxylation of 4 β -hydroxy-4 α -methyl-5 α androstanes by Cephalosporium aphidicola . Phytochemistry 50 : 25 – 30 .

Berrie JR , Williams RAD , Smith KE . 1999 . Microbial transforma-tions of steroids-XI . Progesterone transformation by Streptomy-ces roseochromogenes -purifi cation and characterisation of the

O

O

O

OH

O

O

Aspergillus tamarii

160 rpm, 5 days, 24 °C

O

O

O O

O

O

OH

O

O

OH O

O

O

O

O

O

17α-Hydroxyprogesterone

17α-Oxa-D-homo-androst-1,4-diene-3,17-dione

Testolactone

+

16,17-Epoxyprogesterone 16α,17α-Epoxy-20(R)-hydroxypregna-4-en-3-one

Deoxycorticosterone Testolactone

Aspergillus tamarii

160 rpm, 5 days, 24 °C

Aspergillus tamarii

160 rpm, 5 days, 24 °C

Scheme 8. Lactonization reactions.


16 α - hydroxylase system . J Steroid Biochem Mol Biol 71: 153 – 165 .

Bhatti HN , Khera RA . 2012 . Biological transformations of steroidal compounds: a review . Steroids 77 : 1267 – 1290 .

Bisogno FR , Orden AA , Pranzoni CA , Cifuente DA , Giordano OS , Kurina Sanz M . 2007 . Atypical regioselective biohydrolysis on steroidal oxiranes by Aspergillus niger whole cells: some stereochemical features . Steroids 72 : 643 – 652 .

Borges KB , Borges WS , Duron-Patron R , Pupo MT , Bonato PS , Collado IG . 2009 . Stereoselective biotransformations using fungi as biocatalysts . Tetrahedron Asymmetr 20 : 385 – 397 .

Bortolini O , Medici A , Poli S . 1997 . Biotransformations on ster-oid nucleus of bile acids . Steroids 62 : 564 – 577 .

Bhosale S , Saratale G , Govindwa S . 2006 . Biotransformation enzymes in Cunninghamella blakesleeana (NCIM-687) . J Basic Microb 46 : 444 – 448 .

Boynton J , Hanson JR , Hunter AC . 1997 . The hydroxylation of some 13 α -methylsteroids by Cephalosporium aphidicola . Phytochemistry 45 : 951 – 956 .

Brandenbusch C , Sadowski G . 2010 . Supercritical phase behavior for biotransformation processing . J Supercrit Fluids 55 : 635 – 642 .

Bredeh ö ft M , Baginski R , Parr MK , Thevis M , Sch ä nzer W . 2012 . Investigations of the microbial transformation of cortisol to prednisolone in urine samples . J Steroid Biochem Mol Biol 129 : 54 – 60 .

Brueggemeier RW , Li P-K , Abraham DJ . 2003 . Fundamentals of steroid chemistry and biochemistry . Burger ’ s Medicinal Chem-istry and Drug Discovery. New York: John Wiley & Sons

Burton SG . 2003 . Oxidizing enzymes as biocatalysts . Trends Biotechnol 21 : 543 – 549 .

Cabeza MS , Guti é rrez EB , Garc í a GA , Avalos AH , Hern á ndez MAH . 1999 . Microbial transformations of testo-sterone to 5 α -dihydrotestosterone by two species of Penicillium : P. chrysogenum and P. crustosum . Steroids 64 : 379 – 384 .

Carballeira JD , Quezada MA , Hoyos P , Sime ó Y , Hernaiz MJ , Alcantara AR , Sinisterra JV . 2009 . Microbial cells as catalysts for stereoselective red-ox reactions . Biotechnol Adv 27 : 686 – 714 .

Carvalho F , Marques MPC , de Carvalho CC , Cabral JM , Fernandes P . 2009 . Sitosterol bioconversion with resting cells in liquid polymer based systems . Bioresour Technol 100 : 4050 – 4053 .

Chen K-C , Yin W-S , Tiu C , Houng J-Y . 1994 . 11 α -hydroxylation of progesterone using modifi ed alginate-immobilized cells . Enzyme Microb Technol 16 : 551 – 555 .

Chen K , Tong WY , Wei DZ , Jiang W . 2007 . The 11 β -hydroxylation of 16,17 α -epoxyprogesterone and the purifi cation of the 11 β -hydroxylase from Absidia coerulea IBL02 . Enzyme Microb Technol 41 : 71 – 79 .

Chen ND , Yue L , Zhang J , Kou JP , Yu BY . 2010 . One unique steroidal sapogenin obtained through the microbial transforma-tion of ruscogenin by Phytophthora cactorum ATCC 32134 and its potential inhibitory effect on tissue factor (TF) procoagulant activity . Bioorg Med Chem Lett 20 : 4015 – 4017 .

Choudhary MI , Erum S , Atif M , Malik R , Khan NT , Atta-ur-Rahman . 2011 . Biotransformation of (20 S)-20-hydroxymethylpregna-1,4-dien-3-one by four fi lamentous fungi . Steroids 76 : 1288 – 1296 .

Choudhary MI , Khan NT , Musharraf SG , Anjum S , Atta-ur-Rahman . 2007 . Biotransformation of adrenosterone by fi lamentous fungus, Cunninghamella elegans . Steroids 72 : 923 – 929 .

Choudhary MI , Mohammad MY , Musharraf SG , Parvez M , Al-Aboudi A , Atta-ur-Rahman . 2009 . New oxandrolone deriv-atives by biotransformation using Rhizopus stolonifer . Steroids 74 : 1040 – 1044 .

Choudhary MI , Sultan S , Khan MTH , Rahman A . 2005 . Microbial transformation of 17 α -ethynyl- and 17 α -ethylsteroids, and tyrosinase inhibitory activity of transformed products . Steroids 70 : 798 – 802 .

Collins L , Daugulis A . 1999 . Benzene/toluene/p-xylene degrada-tion . Part I. Solvent selection and toluene degradation in a two-phase partitioning bioreactor. Appl Microbiol Biotechnol 52 : 354 – 359 .

Cotillon A , Morfi n R . 1999 . Transformation of 3-hydroxysteroids by Fusarium moniliforme 7 α -hydroxylase . J Steroid Biochem Mol Biol 68 : 229 – 237 .

Č re š nar B , Ž akelj-Mavri č M . 2009 . Aspects of the steroid response in fungi . Chem Biol Interact 178 : 303 – 309 .

Cruz A , Fernandes P , Cabral J , Pinheiro H . 2001 . Whole-cell biotransformation of β -sitosterol in aqueous-organic two-phase systems . J Mol Catal B Enzym 11 : 579 – 585 .

Cruz A , Fernandes P , Cabral J , Pinheiro H . 2002 . Effect of phase composition on the whole cell bioconversion of β -sitosterol in biphasic medium . J Mol Catal B Enzym 19 – 20 : 371 – 375 .

Dewick P . 2009 . Medicinal natural products: a biosynthetic approach . West Sussex: John Wiley & Sons.

Dong Y , Teng H , Qi S , Liu L , Wang H , Zhao Y , Xiu Z . 2010 . Pathways and kinetics analysis of biotransformation of Dioscorea zingiberensis by Aspergillus oryzae . Biochem Eng J 52 : 123 – 130 .

Donova M , Egorova O . 2012 . Microbial steroid transformations: current state and prospects . Appl Microbiol Biotechnol 94 : 1423 – 1447 .

Donova MV , Egorova OV , Nikolayeva VM . 2005 . Steroid 17 β -reduction by microorganisms – a review . Process Biochem 40 : 2253 – 2262 .

Dray F , Cotillon A . 1999 . 7 α -Hydroxylation of dehydroepiandros-terone and pregnelone by bioconversion using Fusarium moniliforme . Fr Patent 2771105 .

El-Kadi IA , Mostafa ME . 2004 . Hydroxylation of progesterone by some Trichoderma species . Folia Microbiol 49 : 285 – 290 .

Faber K . 2011 . Biotransformations in organic chemistry: a text-book . Berlin: Springer .

Faramarzi MA , Adrangi S , Yazdi MT . 2008a . Microalgal biotrans-formation of steroids . J Phycol 44 : 27 – 37 .

Faramarzi MA , Aghelnejad M , Yazdi MT , Amini M , Hajarolasvadi N . 2008b . Metabolism of androst-4-en-3,17-dione by the fi lamentous fungus Neurospora crassa . Steroids 73 : 13 – 18 .

Faramarzi MA , Badiee M , Yazdi MT , Amini M , Torshabi M . 2008c . Formation of hydroxysteroid derivatives from androst-4-en-3,17-dione by the fi lamentous fungus Mucor racemosus . J Mol Catal B Enzym 50 : 7 – 12 .

Faramarzi MA , Hajarolasvadi N , Yazdi MT , Amini M , Aghelnejad M . 2007 . Microbiological hydroxylation of androst-1,4-dien-3,17-dione by Neurospora crassa . Biocatal Biotrans-form 25 : 72 – 78 .

Faramarzi MA , Sadighi A . 2013 . Insights into biogenic and chem-ical production of inorganic nanomaterials and nanostructures . Adv Colloid Interface Sci 189 – 190 : 1 – 20 .

Faramarzi MA , Tabatabaei Yazdi M , Amini M , Zarrini G , Shafi ee A . 2003 . Microbial hydroxylation of progesterone with Acremonium strictum . FEMS Microbiol Lett 222 : 183 – 186 .

Faramarzi MA , Yazdi MT , Amini M , Mohseni FA , Zarrini G , Amani A , Shafi ee A . 2004 . Microbial production of testosterone and testololactone in the culture of Aspergillusterreus . World J Microbiol Biotechnol 20 : 657 – 660 .

Faramarzi MA , Yazdi MT , Amini M , Shafi ee A . 2008d . Prednisolone bio-transformation in the culture of fi lamentous fungus Acremonium strictum . Biotechnology 7 : 343 – 346 .

Faramarzi MA , Yazdi MT , Jahandar H , Amini M , Monsef-Esfahani HR . 2006 . Studies on the microbial transfor-mation of androst-1,4-dien-3,17-dione with Acremonium strictum . J Ind Microbiol Biotechnol 33 : 725 – 733 .


Faramarzi MA , Yazdi MT , Shafi ee A , Zarrini G . 2002 . Microbial transformation of hydrocortisone by Acremonium strictum PTCC 5282 . Steroids 67 : 869 – 872 .

Faramarzi MA , Zolfaghary N , Yazdi MT , Adrangi S , Rastegar H , Amini M , Badiee M . 2009 . Microbial conversion of androst ‐ 1,4 ‐ dien ‐ 3,17 ‐ dione by Mucor racemosus to hydroxysteroid ‐ 1,4 -dien ‐ 3 ‐ one derivatives . J Chem Technol Biotechnol 84 : 1021 – 1025 .

Fathabad EG , Amini M , Faramarzi M , Yazdi MT . 2006 . Biotrans-formation of Hydrocortisone by Neurospora crassa . J Sci Islam Repub Iran 17 : 309 – 312 .

Fernandes P , Cruz A , Angelova B , Pinheiro HM , Cabral JMS . 2003 . Microbial conversion of steroid compounds: recent developments . Enzyme Microb Technol 32 : 688 – 705 .

Flores E , Cabeza M , Quiroz A , Bratoeff E , Garc í a G , Ram í rez E . 2003 . Effect of a novel steroid (PM-9) on the inhibition of 5 α -reductase present in Penicillium crustosum broths . Steroids 68 : 271 – 275 .

Forootanfar H , Faramarzi MA , Shahverdi AR , Yazdi MT . 2011 . Purifi cation and biochemical characterization of extracellular laccase from the ascomycete Paraconiothyrium variabile . Biore-sour Technol 102 : 1808 – 1814 .

Gao JM , Shen JW , Wang JY , Yang Z , Zhang AL . 2011 . Microbial transformation of 3 β -acetoxypregna-5,16-diene-20-one by Penicillium citrinum . Steroids 76 : 43 – 47 .

Gharaei-Fathabad E , Aroona C . 2011 . Biotransformation of progesterone by Penicillium aurantiogriseum . Res J Microbiol 6 : 98 – 104 .

Ghasemi S , Sadighi A , Heidary M , Bozorgi-Koushalshahi M , Habibi Z , Faramarzi MA . 2013 . Immobilisation of lipase on the surface of magnetic nanoparticles and non-porous glass beads for regioselective acetylation of prednisolone . IET Nanobio-technol 7 : 100 – 108 .

Goetschel R , Bar R . 1992 . Formation of mixed crystals in microbial conversion of sterols and steroids . Enzyme Microb Technol 14 : 462 – 469 .

Groussin A-L , Antoniotti S . 2012 . Valuable chemicals by the enzy-matic modifi cation of molecules of natural origin: terpenoids, steroids, phenolics and related compounds . Bioresour Technol 115 : 237 – 243 .

Han Y , Sun B , Jiang B , Hu X , Spranger MI , Zhang Y , Zhao Y . 2010 . Microbial transformation of ginsenosides Rb1, Rb3 and Rc by Fusarium sacchari . J Appl Microbiol 109 : 792 – 798 .

Hanson JR , Hunter AC . 1998 . The microbiological hydroxylation of some steroids with a cortical side chain by Cephalosporium aphidicola . Phytochemistry 49 : 2359 – 2362 .

Hanson JR , Nasir H , Parvez A . 1996 . The hydroxylation of testosterone and some relatives by Cephalosporium aphidicola . Phytochemistry 42 : 411 – 415 .

He B , Li W . 2013 . Effi cient Production of androstadienedione and testolactone from progesterone by biotransformation using Fusarium solani . Res J Biotech 8 : 56 – 61 .

He X , Liu B , Wang G , Wang X , Su L , Qu G , Yao X . 2006a . Microbial metabolism of methyl protodioscin by Aspergillus niger culture-a new androstenedione producing way from ster-oid . J Steroid Biochem Mol Biol 100 : 87 – 94 .

He X , Tang J , Qiao A , Wang G , Jiang M , Liu RH , Yao X . 2006b . Cytotoxic biotransformed products from cinobufagin by Mucor spinosus and Aspergillus Niger . Steroids 71 : 392 – 402 .

Holland HL . 2008 . Biotechnology set . Weinheim: Wiley-VCH Verlag GmbH .

Holland HL . 1999 . Recent advances in applied and mechanistic aspects of the enzymatic hydroxylation of steroids by whole-cell biocatalysts . Steroids 64 : 178 – 186 .

Holland HL , Lakshmaiah G , Ruddock PL . 1998 . Microbial hydroxylation of acetylaminosteroids . Steroids 63 : 484 – 495 .

Houng JY , Chiang WP , Chen KC , Tiu C . 1994 . 11 α -Hydroxyla-tion of progesterone in biphasic media using alginate-entrapped Aspergillus ochraceus gel beads coated with polyurea . Enzyme Microb Technol 16 : 485 – 491 .

Hu YM , Yu ZL , Fong WF . 2011 . Stereoselective Biotransforma-tion of Timosaponin A-III by Saccharomyces cerevisiae . J Microbiol Biotechnol 21 : 582 – 589 .

Hu S-h, Genain G , Azerad R . 1995 . Microbial transformation of steroids: contribution to 14 α -hydroxylations . Steroids 60 : 337 – 352 .

Huang LH , Li J , Xu G , Zhang XH , Wang YG , Yin YL , Liu HM . 2010 . Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling . Steroids 75 : 1039 – 1046 .

Hunter AC . 2007 . The current chemical utility of marine and terrestrial fi lamentous fungi in side-chain chemistry . Curr Org Chem 11 : 665 – 677 .

Hunter AC , Carragher NE . 2003 . Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus tamarii KITA: transformation of a series of cortical steroid analogues . J Steroid Biochem Mol Biol 87 : 301 – 308 .

Hunter AC , Coyle E , Morse F , Dedi C , Dodd HT , Koussoroplis SJ . 2009 . Transformation of 5-ene steroids by the fungus Aspergillus tamarii KITA: mixed molecular fate in lac-tonization and hydroxylation pathways with identifi cation of a putative 3 β -hydroxy-steroid dehydrogenase/ Δ 5 - Δ 4 isomerase pathway . Biochim Biophys Acta 1791 : 110 – 117 .

Hunter AC , Mills PW , Dedi C , Dodd HT . 2008 . Predominant allylic hydroxylation at carbons 6 and 7 of 4 and 5-ene functionalized steroids by the thermophilic fungus Rhizomucortauricus IMI23312 . J Steroid Biochem Mol Biol 108 : 155 – 163 .

Hunter AC , Rymer SJ , Dedi C , Dodd HT , Nwozor QC , Moghimi SM . 2011 . Transformation of structurally diverse steroidal analogues by the fungus Corynespora cassiicola CBS 161.60 results in generation of 8 β -monohydroxylated metabo-lites with evidence in favour of 8 β -hydroxylation through inverted binding in the 9 α -hydroxylase . Biochim Biophys Acta 1811 : 1054 – 1061 .

Hunter CA , Watts KR , Dedi C , Dodd HT . 2009b . An unusual ring-A opening and other reactions in steroid transformation by the thermophilic fungus Myceliophthora thermophila . J Ster-oid Biochem Mol Biol 116 : 171 – 177 .

Huszcza E , Dmochowska-Gladysz J . 2003a . Transformations of testosterone and related steroids in Absidia glauca culture . J Basic Microbiol 43 : 113 – 120 .

Huszcza E , Dmochowska-G ł adysz J . 2003b . Transformations of testosterone and related steroids by Botrytis cinerea . Phytochem-istry 62 : 155 – 158 .

Irrgang S , Schlosser D , Fritsche W . 1997 . Involvement of cytochrome P-450 in the 15 α -hydroxylation of 13-ethyl-gon-4-ene-3,17-dione by Penicillium raistrickii . J Steroid Biochem Mol Biol 60 : 339 – 346 .

Itagaki E , Iwaya T . 1988 . Purifi cation and Characterization of 17 β -Hydroxysteroid Dehydrogenase from Cylindrocarpon radicicola . J Biochem 103 : 1039 – 1044 .

Janeczko T , Dmochowska-Gładysz J , Kostrzewa-Susłow E , Białońska A , Ciunik Z . 2009 . Biotransformations of steroid compounds by Chaetomium sp. KCH 6651 . Steroids 74 : 657 – 661 .

Junter G , Jouenne T . 2004 . Immobilized viable microbial cells: from the process to the proteome or the cart before the horse . Biotechnol Adv 22 : 633 – 658 .

Kalbasi A , Faramarzi MA , Hejazi MS , Jahandar H , Amini M , Jalali SM . 2009 . 14 α -hydroxylation of androst-4-en-3,17-dione


by the whole cells of cyanobacterium Nostocpiscinale . Biotech-nology 8 : 370 – 374 .

Kardinahl S , Rabelt D , Reschke M . 2006 . Biotransformation: from a vision to the technology! Biotransformation: Von der vision zur technologie! Chem Ing Tech 78 : 209 – 217 .

Ko ł ek T , Szpineter A , Ś wizdor A . 2008 . Baeyer-Villiger oxidation of DHEA, pregnenolone, and androstenedione by Penicillium lilacinum AM111 . Steroids 73 : 1441 – 1445 .

Kristan K , Stojan J , Adamski J , Lani š nik Ri ž ner T . 2007 . Rational design of novel mutants of fungal 17 β -hydroxysteroid dehydro-genase . J Biotechnol 129 : 123 – 130 .

Kulkarni AG , Lele SS , Kulkarni PR . 1998 . Improved adsorption of Aspergillus niger 589 spores on high-density polyethylene for progesterone biotransformation . J Ferment Bioeng 86 : 510 – 512 .

Lamm AS , Chen ARM , Reynolds WF , Reese PB . 2007 . Steroid hydroxylation by Whetzeliniasclerotiorum , Phanerochaete chrysosporium and Mucor plumbeus . Steroids 72 : 713 – 722 .

Leon R , Fernandes P , Pinheiro H , Cabral J . 1998 . Whole cell biocatalysis in organic media . Enzyme Microb Technol 23 : 483 – 500 .

Li H , Liu HM , Ge W , Huang L , Shan L . 2005 . Synthesis of 7 α -hydroxy-dehydroepiandrosterone and 7 β -hydroxy-dehydroepiandrosterone . Steroids 70 : 970 – 973 .

Lin Y , Song X , Fu J , Lin J , Qu Y . 2009 . Microbial transformation of phytosterol in corn fl our and soybean fl our to 4-androstene-3,17-dione by Fusarium moniliforme Sheld . Bioresour Technol 100 : 1864 – 1867 .

Lisowska K , D ł ugonski J . 2003 . Concurrent corticosteroid and phenanthrene transformation byfi lamentous fungus Cunning-hamella elegans . J Steroid Biochem 85 : 63 – 69 .

Liu HM , Li H , Shan L , Wu J . 2006 . Synthesis of steroidal lactone by penicillium citreo-viride . Steroids 71 : 931 – 934 .

Liu JH , Yu BY . 2010 . Biotransformation of bioactive natural prod-ucts for pharmaceutical lead compounds.Curr Org Chem 14 : 1400 – 1406 .

Lloret L , Eibes G , L ú -Chau TA , Moreira MT , Feijoo G , Lema JM . 2010 . Laccase-catalyzed degradation of anti-infl ammatories and estrogens . Biochem Eng J 51 : 124 – 131 .

Lobastova TG , Khomutov SM , Vasiljeva LL , Lapitskaya MA , Pivnitsky KK , Donova MV . 2009 . Synthesis of 3 β -hydroxy-androsta-5,7-dien-17-one from 3 β -hydroxyandrost-5-en-17-one via microbial 7 α -hydroxylation . Steroids 74 : 233 – 237 .

Lu, Deng S , Chen H , Hou J , Zhang B , Tian Y , Wang C , Ma X . 2013 . Microbial transformation of cinobufotalin by Alternaria alternate AS 3.4578 and Aspergillusniger AS 3.739 . J Mol Catal B Enzym 89 : 102 – 107 .

Lu W-Y , Du L-X , Wang M , Wen J-P , Sun B , Guo Y-W . 2006 . Effect of two-steps substrate addition on steroids 11 β -hydroxylation by Curvularia lunata CL-114 . Biochem Eng J 32 : 233 – 238 .

Ma XC , Zheng J , Guo DA . 2007 . Highly selective isomerization and dehydrogenation of three major bufadienolides at 3-OH by Fusarium solani . Enzyme Microb Technol 40 : 1585 – 1591 .

Mahato SB , Banerjee S . 1985 . Steroid transformations by micro-organisms-II . Phytochemistry 24 : 1403 – 1421 .

Mahato SB , Banerjee S , Podder S . 1989 . Steroid transformations by microorganisms-III . Phytochemistry 28 : 7 – 40 .

Mahato SB , Garai S . 1997 . Advances in microbial steroid biotrans-formation . Steroids 62 : 332 – 345 .

Mahato SB , Mukherjee A . 1984 . Steroid transformations by microorgamisms . Phytochemistry 23 : 2131 – 2154 .

Malaviya A , Gomes J . 2008 . Enhanced biotransformation of sitosterol to androstenedione by Mycobacterium sp. using cell wall permeabilizing antibiotics . J Ind Microbiol Biotechnol 35 : 1235 – 1239 .

Manosroi A , Saowakhon S , Manosroi J . 2008 . Enhancement of androstadienedione production from progesterone by biotrans-

formation using the hydroxypropyl- β -cyclodextrin complexa-tion technique . J Steroid Biochem Mol Biol 108 : 132 – 136 .

Manosroi J , Saowakhon S , Manosroi A . 2007 . A novel one-step biotransformation of cortexolone-21-acetate to hydrocortisone acetate using Cunninghamella blakesleeana ATCC 8688a . Enzyme Microb Technol 41 : 322 – 325 .

Marques MPC , Carvalho F , de Carvalho CCCR , Cabral JMS , Fernandes P . 2010 . Steroid bioconversion: towards green proc-esses . Food Bioprod Process 88 : 12 – 20 .

McAdam EJ , Bagnall JP , Koh YKK , Chiu TY , Pollard S , Scrimshaw MD , Lester JN , Cartmell E . 2010 . Removal of steroid estrogens in carbonaceous and nitrifying activated sludge processes . Chemosphere 81 : 1 – 6 .

Mindnich R , M ö ller G , Adamski J . 2004 . The role of 17 β -hydroxysteroid dehydrogenases . Mol Cell Endocrinol 218 : 7 – 20 .

Mogharabi M , Faramarzi MA . 2014 . Laccase and laccase-mediated systems in the synthesis of organic compounds . Adv Synth Catal 356 : 897 – 927 .

Mogharabi M , Nassiri-Koopaei N , Bozorgi-Koushalshahi M , Nafi ssi-Varcheh N , Bagherzadeh G , Faramarzi MA . 2012 . Immobilization of laccase in alginate-gelatin mixed gel and decolorization of synthetic dyes . Bioinorg Chem Appl 2012 : 6, article no. 823830 .

Mohammad MY , Musharraf SG , Al-Majid AM , Atta-ur-Rahman, Choudhary MI . 2013 . Biotransformation of mestanolone and 17-methyl-1-testosterone by Rhizopus stolonifer . Biocatal Biotransform 31 : 153 – 159 .

Murray RK . 2000 . Harper ’ s biochemistry . Stamford: Appleton & Lange .

Nassiri-Koopaei N , Mogharabi M , Amini M , Shafi ee A , Faramarzi MA . 2013 . Fungal transformation of methyltestosterone by the soil ascomycete Acremonium strictum to some hydroxyderivatives of 17-methylsteroid . Chem Nat Compd 49 : 665 – 670 .

Ni Y , Chen R . 2004 . Accelerating whole cell biocatalysis by reducing outer membrane permeability barrier . Biotechnol Bioeng 87 : 804 – 811 .

Nikolova P , Ward OP . 1992 . Whole cell yeast biotransformations in two-phase systems: effect of solvent on product formation and cell structure . J Ind Microbiol Biotechnol 10 : 169 – 177 .

Pajic T , Vitas M , Zigon D , Pavko A , Kelly SL , Komel R . 1999 . Biotransformation of steroids by the fi ssion yeast Schizosaccharomyces pombe . Yeast 15 : 639 – 645 .

Paraszkiewicz K , D ł ugo ń ski J . 1998 . Cortexolone 11 β -hydroxylation in protoplasts of Curvularia lunata . J Biotechnol 65 : 217 – 224 .

Paraszkiewicz K , Kanwal A , D ł ugo ń ski J . 2002 . Emulsifi er production by steroid transforming fi lamentous fungus Curvularia lunata Growth and product characterization . J Biotechnol 92 : 287 – 294 .

Peart PC , Chen ARM , Reynolds WF , Reese PB . 2012 . Entrap-ment of mycelial fragments in calcium alginate: a general technique for the use of immobilized fi lamentous fungi in biocatalysis . Steroids 77 : 85 – 90 .

Peart PC , McCook KP , Russell FA , Reynolds WF , Reese PB . 2011 . Hydroxylation of steroids by Fusarium oxysporum , Exophiala jeanselmei and Ceratocystis paradoxa . Steroids 76 : 1317 – 1330 .

Pervaiz I , Ahmad S , Madni MA , Ahmad H , Khaliq FH . 2013 . Microbial biotransformation: a tool for drug designing . Appl Biochem Microb 49 : 437 – 450 .

Petri č Š , Hakki T , Bernhardt R , Ž igon D , Č re š nar B . 2010 . Discovery of a steroid 11 α -hydroxylase from Rhizopus oryzae and its biotechnological application . J Biotechnol 150 : 428 – 437 .

Quezada MA , Carballeira JD , Garc í a-Burgos CA , Sinisterra JV . 2008 . Monascus kaoliang CBS 302.78 immobilized in tailor-


made agars as catalyst for reduction of ketones: on the quest for a green biocatalyst . Process Biochem 43 : 1220 – 1226 .

Riva S . 2001 . Biocatalytic modifi cation of natural products . Curr Opin Chem Biol 5 : 106 – 111 .

Ri ž ner TL , Adamski J , Ž akelj – Mavri č M . 2001 . Expression of 17 β -hydroxysteroid dehydrogenases in mesophilic and extremophilic yeast . Steroids 66 : 49 – 54 .

Ri ž ner TL , Ž akelj-Mavri č M , Plemenita š A , Zorko M . 1996 . Purifi cation and characterization of 17 β -hydroxysteroid dehy-drogenase from the fi lamentous fungus Cochliobolus lunatus . J Steroid Biochem Mol Biol 59 : 205 – 214 .

Romano A , Romano D , Ragg E , Costantino F , Lenna R , Gandolfi R , Molinari F . 2006 . Steroid hydroxylations with Botryodiplodia malorum and Colletotrichum lini . Steroids 71 : 429 – 434 .

Saab HB , Fouchard S , Boulanger A , Llopiz P , Neunlist S . 2010 . Performance of Luffa cylindrica as an immobilization matrix for the biotransformation of cholesterol by Mycobacterium species . Biocatal Biotransform 28 : 387 – 394 .

Santhanam HK , Shreve GS . 1994 . Solvent selection and produc-tivity in multiphase biotransformation systems . Biotechnol Prog 10 : 187 – 192 .

Schmauder HP , Schlosser D , G ü nther T , Hattenbach A , Sauerstein J , Jungnickel F , Augsten H . 1991 . Application of immobilized cells for biotransformations of steroids . J Basic Microb 31 : 453 – 477 .

Schlosser D , Irrgang S , Schmauder HP . 1993 . Steroid hydroxyla-tion with free and immobilized cells of Penicillium raistrickii in the presence of β -cyclodextrin . Appl Microbiol Biotechnol 39 : 16 – 20 .

Shahidi NT . 2001 . A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids . Clin Ther 23 : 1355 – 1390 .

Siddiqui MS , Thodey K , Trenchard I , Smolke CD . 2012 . Advanc-ing secondary metabolite biosynthesis in yeast with synthetic biology tools . FEMS Yeast Res 12 : 144 – 170 .

Silva CP , Otero M , Esteves V . 2012 . Processes for the elimination of estrogenic steroid hormones from water: a review . Environ Pollut 165 : 38 – 58 .

Silva MMC , Carvalhoa JF , Riva S , S á e Melo ML . 2011 . Biocatalytic transformations of steroids: focus on hydrolase-catalyzed reactions . Curr Org Chem 15 : 928 – 941 .

Simard J , Ricketts ML , Gingras S , Soucy P , Feltus FA , Melner MH . 2005 . Molecular biology of the 3 β -hydroxysteroid dehydrogenase/ Δ 5 - Δ 4 isomerase gene family . Endocr Rev 26 : 525 – 582 .

Singer Y , Shity H , Bar R . 1991 . Microbial transformations in a cyclodextrin medium . Part 2. Reduction of androstenedione to testosterone by Saccharomyces cerevisiae . Appl Microbiol Biotechnol 35 : 731 – 737 .

Smith K , Kirk D , Latif S . 1989 . Microbial transformation of steroids-II . Transformation of progesterone, testosterone and androstenedione by Phycomyces blakesleeanus . J Steroid Biochem 32 : 445 – 451 .

Smith KE , Ahmed F , Williams RAD , Kelly SL . 1994 . Microbial transformations of steroids - VIII . Transformation of progester-one by whole cells and microsomes of Aspergillus fumigatus . J Steroid Biochem Mol Biol 49 : 93 – 100 .

Stefan A , Palazzo G , Ceglie A , Panzavolta E , Hochkoeppler A . 2002 . Water-in-Oil microemulsions to sustain long term viabil-ity of microbial cells in organic solvents . Biotechnol Bioeng 81 : 323 – 328 .

Suzuki K , Sanga K-i, Chikaoka Y , Itagaki E . 1993 . Purifi cation and properties of cytochrome P-450 (P-450lun) catalyzing ster-oid 11 β -hydroxylation in Curvularia lunata . Biochim Biophys Acta Protein Struct Mol Enzymol 1203 : 215 – 223 .

Ś wizdor A , Ko ł ek T . 2005 . Transformations of 4- and 17 α -substituted testosterone analogues by Fusarium culmorum . Steroids 70 : 817 – 824 .

Ś wizdor A , Ko ł ek T , Panek A , Bia ł o ń ska A . 2011 . Microbial Baeyer-Villiger oxidation of steroidal ketones using Beauveria bassiana : Presence of an 11 α -hydroxyl group essential to gen-eration of D-homo lactones . Biochim Biophys Acta 1811 : 253 – 262 .

Tamagawa Y , Yamaki R , Hirai H , Kawai S , Nishida T . 2006 . Removal of estrogenic activity of natural steroidal hormone estrone by ligninolytic enzymes from white rot fungi . Chemo-sphere 65 : 97 – 101 .

Tin MK , Hakki T , Bernhardt R . 2011 . Fission yeast Schizosac-charomycespombe as a new system for the investigation of corti-costerone methyloxidase defi ciency-causing mutations . J Steroid Biochem Mol Biol 124 : 31 – 37 .

Tong WY , Dong X . 2009 . Microbial biotransformation: recent developments on steroid drugs . Recent Pat Biotechnol 3 : 141 – 153 .

Torshabi M , Badiee M , Faramarzi MA , Rastegar H , Forootanfar H , Mohit E . 2011 . Biotransformation of methyl-testosterone by the fi lamentous fungus Mucorracemosus . Chem Nat Compd 47 : 59 – 63 .

Ueda M , Shintani K , Nakanishi-Anjyuin A , Nakazawa M , Kusuda M , Nakatani F , Kawaguchi T , Tsujiyama S , Kawanishi M , Yagi T , Miyatake K . 2012 . A protein from Pleurotus eryngii var. tuoliensis C.J . Mou with strong removal activity against the natural steroid hormone, estriol: purifi ca-tion, characterization, and identifi cation as a laccase. Enzyme Microb Technol 51 : 402 – 407 .

Venisetty RK , Ciddi V . 2003 . Application of microbial biotrans-formation for the new drug discovery using natural drugs as substrates . Curr Pharm Biotechnol 4 : 153 – 167 .

Vico P , Cauet G , Rose K , Lathe R , Degryse E . 2002 . Dehydroe-piandrosterone (DHEA) metabolism in Saccharomyces cerevisiae expressing mammalian steroid hydroxylase CYP7B: ayr1p and Fox2p display 17 β -hydroxysteroid dehydrogenase activity . Yeast 19 : 873 – 886 .

Vitas M , Paji č T , L. Kelly S, Komel R . 1997 . 11 β -Hydroxysteroid dehydrogenase activity in progesterone biotransformation by the fi lamentous fungus Cochliobolus lunatus . J Steroid Biochem 63 : 345 – 350 .

Wang J , Chen C , Li B , Zhang J , Yu Y . 1998 . Production of Hydrocortisone from Cortexolone-21-Acetate by Immobilized Absidia orchidis in Cosolvent-Containing Media . Enzyme Microb Technol 22 : 368 – 373 .

Wang Z , Dai Z . 2010 . Extractive microbial fermentation in cloud point system . Enzyme Microb Technol 46 : 407 – 418 .

Wang Y , Sun Y , Wang C , Huo X , Liu P , Wang C , Zhang B , Zhan L , Zhang H , Deng S , Zhao Y , Ma X . 2013a . Biotransformation of 11-keto- β -boswellic acid by Cunninghamella blakesleana . Phytochemistry 96 : 330 – 336 .

Wang Y , Sun D , Chen Z , Ruan H , Ge W . 2013b . Biotransforma-tion of 3 β -hydroxy-5-en-steroids by Mucor silvaticus . Biocatal Biotransform 31 : 168 – 174 .

Wang Z , Xu J-H , Chen D . 2008 . Whole cell microbial transforma-tion in cloud point system . J Ind Microbiol Biotechnol 35 : 645 – 656 .

Wang Z , Zhao F , Hao X , Chen D , Li D . 2004a . Microbial trans-formation of hydrophobic compound in cloud point system . J Mol Catal B Enzym 27 : 147 – 153 .

Wang Z , Zhao F , Hao X , Chen D , Li D . 2004b . Model of bioconversion of cholesterol in cloud point system . Biochem Eng J 19 : 9 – 13 .

Wang Z , Zhao F , Hao X , Chen D , Li D . 2005 . Cloud point system as a tool to improve the effi ciency of biotransformation . Enzyme Microb Technol 36 : 589 – 594 .

Wang ZF , Huang YL , Rathman JF , Yang ST . 2002 . Lecithin-enhanced biotransformation of cholesterol to androsta-1,4-diene-3,17-dione and androsta-4-ene-3,17-dione . J Chem Technol Biotechnol 77 : 1349 – 1357 .


Whittall J , Sutton P . 2010 . Practical methods for biocatalysis and biotransformations . West Sussex: John Wiley & Sons .

Wilson MR , Gallimore WA , Reese PB . 1999 . Steroid transforma-tions with Fusarium oxysporum var. cubense and Colletotrichum musae . Steroids 64 : 834 – 843 .

Wolken WAM , Tramper J , van der Werf MJ . 2003 . What can spores do for us? Trends Biotechnol 21 : 338 – 345 .

Wu D-X , Guan Y-X , Wang H-Q , Yao S-J . 2011 . 11 α -Hydroxylation of 16 α ,17-epoxyprogesterone by Rhizopus nigricans in a bip-hasic ionic liquid aqueous system . Bioresour Technol 102 : 9368 – 9373 .

Wuts PGM , Anderson AM , Ashford SW , Goble MP , White MJ , Beck D , Gilbert I , Hrab RE . 2008 . A chemobiological synthesis of eplerenone . Synlett 3 : 418 – 422 .

Yang J , Yang S , Yang YL , Zheng H , Weng L , Liu L . 2007 . Microbial hydroxylation of 16 α ,17 α -dimethyl-17 β -(l-oxopropyl)androsta-l,4-dien-3-one to rimexolone by Curvularia lunata AS 3.4381 . J Mol Catal B Enzym 47 : 155 – 158 .

Yang K , Li X-J , Wang J-F , Duan S-D , Zhang L . 2001 . Relationship between growth and morphology of Metarrhizium anisopliae in biotransformation of steroid . T Tianjin U 7 : 1 – 6 .

Yazdi MT , Hosseini S . 2002 . Preparation of Testosterone using micro-bial metabolite of Cholesterol . Daru J Pharm Sci 10 : 70 – 73 .

Yazdi MT , Amani A , Faramarzi MA , Amini M , Shafi ee A , Fathabad EG . 2005 . Nandrolone decanoate transformation by Neurospora crassa . Pharm Biol 43 : 630 – 635 .

Yazdi MT , Zanjanian SM , Faramarzi MA , Amini M , Amani A , Abdi K . 2006 . Microbial transformation of nandrolone decanoate by Acremonium strictum . Arch Pharm 339 : 473 – 476 .

Ye M , Qu G , Guo H , Guo D . 2004 . Novel cytotoxic bufadieno-lides derived from bufalin by microbial hydroxylation and their structure – activity relationships . J Steroid Biochem 9 : 87 – 98 .

Ye M , Qu G , Guo H , Guo D . 2004 . Specifi c 12 β -Hydroxylation of Cinobufagin by Filamentous Fungi . Appl Environ Microb 70 : 3521 – 3527 .

Zafar S , Choudhary MI , Dalvandi K , Mahmood U , Ul-Haq Z . 2013 . Molecular docking simulation studies on potent butyrylcholinesterase inhibitors obtained from microbial trans-formation of dihydrotestosterone . Chem Cent J 7 : 164 .

Zhang X , Ye M , Dong YH , Hu HB , Tao SJ , Chen GT , Yin J , Guo DA . 2011 . Biotransformation of arenobufagin and cinobufota-lin by Alternaria alternata . Biocatal Biotransform 29 : 96 – 101 .

Zhang H , Ren J , Wang Y , Sheng C , Wu Q , Diao A , Zhu D . 2013 . Effective multi-step functional biotransformations of steroids by a newly isolated Fusarium oxysporum SC1301 . Tetrahedron 69 : 184 – 189 .

Ž nidar š i č P , Komel R , Pavko A . 1998 . Studies of a pelleted growth form of Rhizopus nigricans as a biocatalyst for progesterone 11 α -hydroxylation . J Biotechnol 60 : 207 – 216 .

Ž nidar š i č -Plazl, Plazl P . 2010 . Development of a continuous steroid biotransformation process and product extraction within microchannel system . Catal Today 157 : 315 – 320 .

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Recent developments in the fungal transformation of steroids

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