First Seminar on Synthetic Biology for Biotechnology Decision Makers
Transcript of First Seminar on Synthetic Biology for Biotechnology Decision Makers
I I C A H E A D Q U A R T E R S , C O S T A R I C A 1 6 T H A N D 1 7 T H M A R C H , 2 0 1 6
FIRST SEMINAR ON SYNTHETIC BIOLOGY FOR BIOTECHNOLOGY DECISION MAKERS
SYNBIO INDUSTRIAL APPLICATIONS NATALIA VERZA
STATE UNIVERSITY OF CAMPINAS, BRAZIL
WHAT IS SYNTHETIC BIOLOGY?
• Synthetic biology is the engineering of
biology: the synthesis of complex, biologically
based (or inspired) systems, which display functions
that do not exist in nature
• may be applied at all levels of the hierarchy of
biological structures – from individual molecules
to whole cells, tissues and organisms
• enable the design of ‘biological systems’ in a
rational, standardized and systematic way
Source: Synthetic Biology: Applying Engineering to Biology. Molecular Systems Biology (2007) 3:158
WHAT IS SYNTHETIC BIOLOGY?
Synthetic biology aims to use modular, well-
characterized biological parts to predictably
construct novel genetic devices and complex cell-
based systems following engineering principles (Drew
Endy, 2005)
Synthetic Biology Open Language (SBOL)
WHAT IS SYNTHETIC BIOLOGY?
• Synthetic biology aims to make biology
easier to engineer. Synthetic biology is the
convergence of advances in chemistry,
biology, computer science, and
engineering that enables us to go from idea
to product faster, cheaper, and with greater
precision than ever before
Source: SYNTHETIC BIOLOGY ENGINEERING RESEARCH CENTER (SynBerc, NSF, USA)
SYNBIO X GENETIC ENGINEERING WHAT ARE THE DIFFERENCES?
Species of interest: maize calli (Zea mays)
Goal: improve crop tolerance to drought stress
Target gene Co-chaperonin GroES
Donor species: Clostridium acetobutylicum (anaerobic
bacterium)
Codon usage divergences
SYNBIO X GENETIC ENGINEERING WHAT ARE THE DIFFERENCES?
Target gene Co-chaperonin GroES
Donor species: Clostridium acetobutylicum (anaerobic
bacterium)
Anaerobic chamber
Gene amplification and isolation
Construction of DNA expression
cassete
2X35S BlpR
TVSP TEV NptR
UbiPro
T35S
Act1F
Zea mays calli
transformation
Classic genetic engineering Special equipment and new protocols
Methods development and validation
SYNBIO X GENETIC ENGINEERING WHAT ARE THE DIFFERENCES?
Construction of DNA cassette
2X35S BlpR
TVSP TEV NptR
UbiPro
T35S
Act1F
Zea mays calli transformation
Synthetic biology
Design and order optimized, synthetic gene
Target gene Co-chaperonin GroES
Donor species: Clostridium acetobutylicum (anaerobic
bacterium)
SYNBIO X GENETIC ENGINEERING WHAT ARE THE DIFFERENCES?
“Synthetic biology is not an entirely new science. Rather,
aspects of it are an outgrowth of what plant and animal
breeders have been doing for thousands of years and
genetic engineers have been doing for decades—mixing
and matching genetic material with the goal of “creating”
novel plants and animals with desirable traits. What
differentiates synthetic biology from genetic engineering is its
goal of designing new genetic systems and organisms using
standardized parts from the “ground up.”
The Science and Applications of Synthetic and Systems Biology: Workshop Summary
SYNBIO – STATE OF SCIENCE
• In 2006, Dr. Jay Keasling, director of the Berkeley Center for Synthetic
Biology and CEO of the Joint BioEnergy Institute, and three post-
doctoral researchers discovered and re-engineered a yeast
containing bacterial and wormwood genes into a chemical factory to
produce a precursor to artemisinin for use as an inexpensive anti-
malarial drug. The breakthrough originated the Biotech company
Amyris (CA, USA)
Oil-producing yeast under the microscope
SYNBIO – STATE OF SCIENCE
Amyris multi-products platform
SYNBIO – STATE OF SCIENCE
Nature Reviews Microbiology 12, 355–367 (2014)
doi:10.1038/nrmicro3240
Iterative cycle of testing
and learning that spins
faster with help of
synbio tools
SYNBIO – STATE OF SCIENCE
• In May 2010, researchers at the JCVI published the
first functional, self-replicating bacterium whose
entire nuclear genome had been synthesized
artificially in the laboratory, albeit using a naturally
occurring genome sequence as a template
(Gibson et al., 2010).
SYNBIO – STATE OF SCIENCE
• The CRISPR revolution – editing genomes in vivo. The CRISPR/Cas9
technique, derived from a microbial defense system, has enormous
potential application, including altering the germline of humans,
animals and other organisms, and modifying the genes of food crops.
Genome editing was selected by Nature Methods as the 2011 Method
of the Year, and CRISPR-Cas system was selected by Science
Magazine as 2015 Breakthrough of the Year
Emmanuelle Charpentier Max-Plank Institute, Germany
Jennifer Doudna
University of California, Berkeley
SYNBIO – STATE OF SCIENCE
Source: http://www.livemint.com; UC Berkeley
In vivo
genome
editing
INDUSTRIAL SYNBIO MAIN DEVELOPERS
Leading consumer biotech companies building novel biological systems
for bioproducts, biofuels, and the healthcare sector
INDUSTRIAL SYNBIO MAIN DEVELOPERS
Genome-editing technology companies
Companies developing efficient methods to create engineered microbes
to order
Companies that sell synthetic DNA (oligonucleotides, genes, genomes,
genome editing tools)
INDUSTRIAL SYNBIO: POTENTIAL FOR COMMERCIAL PRODUCTS
• BioIsoprene™ - fermentation – based synthetic rubber
made by engineered microbes expressing plant
genes. Synthetic biology has enabled the construction
of a gene that encodes the same amino acid
sequence as the plant enzyme but that is optimized
for expression in the engineered microorganism of
choice (DuPont and The Goodyear Tire & Rubber
Company)
• Cephalexin, a synthetic antibiotic. Starting with a
penicillin-producing microbial strain, DSM introduced
and optimized two enzyme-encoding genes for a
one-step direct fermentation of adipoyl-7-ADCA,
which is converted into Cephalexin via two enzymatic
steps. (DSM)
INDUSTRIAL SYNBIO: POTENTIAL FOR COMMERCIAL PRODUCTS
• Sitagliptin (dipeptidyl peptidase-4 inhibitor
to treat for type II diabetes). Codexis and
Merck collaborated to develop a novel,
environmentally benign alternative
manufacturing route. Using synthetic
biology and its directed evolution
technologies, Codexis discovered and
developed a transaminase capable of
enabling the new biocatalytic route,
which is currently in scale-up towards
commercial manufacture
INDUSTRIAL SYNBIO: POTENTIAL FOR COMMERCIAL PRODUCTS
• BioAcrylic - fermentation – based acrylic
from sugar feedstock — OPX Biotech
partnering with the Dow Chemical
Company(OPX – Cargill and Dow
Chemical)
• BiofeneTM –the Amyris-brand farnesene, a
hydrocarbon building block that can
replace petrochemicals in a wide variety
of products in the cosmetics, flavors and
fragrances, consumer product, polymers,
lubricants and fuel markets (Amyris)
BIO-FUELS PIPELINE PRODUCTS (BY ORGANIZATIONS)
Source: Presidential Commission for the Study of Bioethical Issues (Transparency Market Research Report)
INDUSTRIAL SYNBIO: POTENTIAL FOR COMMERCIAL PRODUCTS
• BDO - 1,4-butanediol, a solvent and in the
manufacture of some types of plastics, elastic
fibers and polyurethanes. Genomatica’s GENO
BDO™ process has been licensed by BASF and
by Novamont; BASF has announced its first
commercial production; over nine million
pounds have been produced to date
• GM Mosquitos – Oxitec’s (Intrexon)solution for
controlling harmful insect populations through
the production of ‘sterile’, self-limiting insects
whose offspring do not survive. Intrexon will
further use Oxitec’s technology to combat
diseases and agricultural pests worldwide
INDUSTRIAL SYNBIO: POTENTIAL FOR COMMERCIAL PRODUCTS
• Plants as bio-factories - Scientists at the
John Innes Centre in the UK have
developed technology for the rapid
expression of proteins in plants. Medicago
Inc. licensed the technology to produce
10M doses of H1N1 swine flu VLP Vaccine in
just a month, outperforming the traditional
method which takes 9-12 months
TECHNOLOGIES AND APPLICATIONS
SynBio enabling technologies
• Enabling Technologies
• Bioinformatics
• Gene Synthesis
• Genome Engineering
• Microfluidics
• Measurement and Modeling
• Nanotechnology
• Cloning and Sequencing
• Site-saturation Mutagenesis
• Enabled Technologies
• Pathway Engineering
• Next-generation Sequencing
SynBio applications
• Environmental Application
• Bioremediation
• Whole-cell Biosensors
• Medical Application
• Artificial Tissue and Tissue
Regeneration
• Drug Discovery and Therapeutics
• Pharmaceuticals
• Industrial Application
• Biofuels and Renewable Energy
• Biomaterials and Green
Chemicals
• Industrial Enzymes
SYNBIO MARKET SEGMENTATION
Source: Transparency Market Research Report, 2013-2019
2009 – 2015 INVESTMENT IN SYNBIO COMPANIES
Source: SynBio Beta
2009 – 2015 SYNBIO COMPANIES FUNDED
Source: SynBio Beta
2015 INVESTMENT IN SYNBIO COMPANIES
Source: SynBio Beta
SYNBIO REGULATION IS NEEDED
• In our view, synthetic biology is an extension of the continuum of genetic science that has been used safely for more than 40 years by the biotechnology industry in the development of commercial products. Examples of synthetic biology use by biotechnology companies illustrate the potential to substantially reduce research and development time and to increase speed to market (Erickson et al. Science (2011)Vol 333, Issue 6047:1254-1256)
• NIH has assessed its “Guidelines for Research Involving Recombinant DNA” with regard to synthetic biology and found that the distinction between recombinant and synthetic techniques is immaterial in discerning the need for biosafety oversight. Rather it is the biological attributes of the final product that should be taken into account.