Journal of Biotechnology & Biomaterials · Significant improvements in microbial amino acid...

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Volume 3 • Issue 2 • 1000e118 J Biotechnol Biomater ISSN:2155-952X JBTBM an open access journal Editorial Open Access *Corresponding author: Hiroshi Yoneyama, Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Japan, Tel: 81-22- 717-8915; Fax: 81-22-717-8707; E-mail: [email protected] Received February 27, 2013; Accepted February 28, 2013; Published March 05, 2013 Amino Acid Exporter: A Tool for the Next-Generation Microbial Fermentation Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Japan Amino acids are important biomaterials for the food, chemical, pharmaceutical, and cosmetic industries. e world market for amino acids is steadily growing and predicted to go over US$ 10 billion within a few years [1, 2]. Of the twenty proteogenic amino acids, essential amino acids, such as lysine, methionine, threonine, and tryptophan which are not synthesized in animals, constitute a major end-use market as feed additives with the largest share of the total amino acid market [3]. Glutamic acid, a sodium salt of which (mono-sodium glutamate) is extensively used in food as a flavour-enhancer, has the largest production amounting to approximately two million tons per year [4]. e above mentioned producer strain breeding is fundamentally based on a wealth of knowledge about biochemistry and genetics of amino acid biosynthetic pathways including their regulation and of their catabolism. e process of amino acid fermentation consists of three parts: i) uptake of carbon and energy sources from the extracellular milieus, ii) metabolic changes of the substrates to intermediates and eventually to products, and iii) efflux of the end-products, amino acids, into medium. e former two aspects, in particular metabolic changes, have been the targets for the development of hyper-producing strains, but the last step has never so far received attention, in part, due to a lack of knowledge about the amino acids efflux systems. Significant improvements in microbial amino acid fermentation have been achieved by the strategies described above, but the productivity comes near to a limit. us, identification and characterization of the amino acid exporters appear to be of particular importance for further development of bacterial strains with much higher productivity. References 1. Global Industry Analysts (2012) Amino acids: A global strategic business report. 2. Ziggers D (2011) Report: Global amino acids market to reach $11.6 billion by 2015. All About Feed. 3. Leuchtenberger W, Huthmacher K, Drauz K (2005) Biotechnological production of amino acids and derivatives: current status and prospects. Appl Microbiol Biotechnol 69: 1-8. 4. Kojima H, Yasueda H (2011) A new frontier of amino acid fermentation: metabolic pathway design and advanced fermentation technology. International Union of Microbiological Societies 2011 Congress (IUMS 2011 Congress), Sapporo, Japan. 5. Kinoshita S, Udaka S, Shimono M (1957) Studies on the amino acid fermentation. J Gen Appl Microbiol 3: 193-205. 6. Kramer R (1996) Genetic and physiological approaches for the production of amino acids. Journal of Biotechnology 45: 1-21. 7. Ikeda M, Ohnishi J, Hayashi M, Mitsuhashi S (2006) A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production. J Ind Microbiol Biotechnol 33: 610-615. 8. Vrljic M, Sahm H, Eggeling L (1996) A new type of transporter with a new type of a cellular function: L-lysine export from Corynebacterium glutamicum. Mol Microbiol 22: 815-826. 9. Hori H, Yoneyama H, Tobe R, Ando T, Isogai E, et al. (2011) Inducible L-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli. Appl Environ Microbiol 77: 4027-4034. Seryoung and Yoneyama, J Biotechnol Biomater 2013, 3:1 DOI: 10.4172/2155-952X.1000e118 Kim Seryoung and Hiroshi Yoneyama* Citation: Seryoung K, Yoneyama H (2013) Amino Acid Exporter: A Tool for the Next-Generation Microbial Fermentation. J Biotechnol Biomater 3: e118. doi:10.4172/2155-952X.1000e118 Copyright: © 2013 Seryoung K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In this context, the molecular mechanism of amino acids export has long been unknown until the lysE gene was identified to encode L-lysine exporter, LysE, in C. glutamicum [8]. Interestingly, LysE also exports L-arginine. Aſter this prominent work, more than ten membrane proteins have appeared to export amino acids and their analogues in C. glutamicum and Escherichia coli, substrates of which are L-isoleucine, L-glutamic acid, L-threonine, L-cysteine, L-leucine, L-valine, and L-aromatic amino acids. In addition to these exporters, L-alanine exporter AlaE (formerly YgaW) has recently been identified in E. coli [9]. e existence of amino acid exporters raises an important question of why bacterial cells possess these transporters to export L-amino acids Amino acid fermentation was triggered in 1957 by the discovery of the soil bacterium, Corynebacterium glutamicum, which produces large amounts of glutamic acid in culture medium [5]. Since then, efforts to produce various amino acids by microbial fermentation resulted in the development of cost-effective strains with extremely high productivity. e early strategies for obtaining such a high producer strain were based on mutagenesis and screening, called metabolic engineering, which lead to changes in metabolic flow toward a certain amino acid of interest mainly by deregulation of the amino acid biosynthetic pathway [6]. As a next step, genetic engineering has been employed recombinant DNA techniques to improve productivity by cloning a gene that encodes a rate-limiting enzyme along the biosynthetic pathway of the amino acid, or by introducing beneficial mutant alleles into the chromosome of a wild-type background strain [7]. at the expense of energy, despite the facts that they are anabolic, but not catabolic, primary metabolites and also are important building blocks of proteins. e answer to this question will be obtained through in-depth understanding of the molecular mechanism of substrate excretion by these exporters and of their regulation. Furthermore, studies on the novel aspects of amino acid metabolism, that is export, will pave the way for the next generation amino acid fermentation technology. J o u r n a l o f B i o t e c h n o l o g y & B i o m a t e r i a l s ISSN: 2155-952X Journal of Biotechnology & Biomaterials

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Page 1: Journal of Biotechnology & Biomaterials · Significant improvements in microbial amino acid fermentation have been achieved by the strategies described above, but the productivity

Volume 3 • Issue 2 • 1000e118J Biotechnol BiomaterISSN:2155-952X JBTBM an open access journal

Editorial Open Access

*Corresponding author: Hiroshi Yoneyama, Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Japan, Tel: 81-22-717-8915; Fax: 81-22-717-8707; E-mail: [email protected]

Received February 27, 2013; Accepted February 28, 2013; Published March 05, 2013

Amino Acid Exporter: A Tool for the Next-Generation Microbial Fermentation

Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Japan

Amino acids are important biomaterials for the food, chemical, pharmaceutical, and cosmetic industries. The world market for amino acids is steadily growing and predicted to go over US$ 10 billion within a few years [1, 2]. Of the twenty proteogenic amino acids, essential amino acids, such as lysine, methionine, threonine, and tryptophan which are not synthesized in animals, constitute a major end-use market as feed additives with the largest share of the total amino acid market [3]. Glutamic acid, a sodium salt of which (mono-sodium glutamate) is extensively used in food as a flavour-enhancer, has the largest production amounting to approximately two million tons per year [4].

The above mentioned producer strain breeding is fundamentally based on a wealth of knowledge about biochemistry and genetics of amino acid biosynthetic pathways including their regulation and of their catabolism. The process of amino acid fermentation consists of three parts:

i) uptake of carbon and energy sources from the extracellularmilieus, ii) metabolic changes of the substrates to intermediates and eventually to products, and iii) efflux of the end-products, amino acids, into medium. The former two aspects, in particular metabolic changes, have been the targets for the development of hyper-producing strains, but the last step has never so far received attention, in part, due to a lack of knowledge about the amino acids efflux systems. Significant improvements in microbial amino acid fermentation have been achieved by the strategies described above, but the productivity comes near to a limit. Thus, identification and characterization of the amino acid exporters appear to be of particular importance for further development of bacterial strains with much higher productivity.

References

1. Global Industry Analysts (2012) Amino acids: A global strategic business report.

2. Ziggers D (2011) Report: Global amino acids market to reach $11.6 billion by 2015. All About Feed.

3. Leuchtenberger W, Huthmacher K, Drauz K (2005) Biotechnological production of amino acids and derivatives: current status and prospects. Appl Microbiol Biotechnol 69: 1-8.

4. Kojima H, Yasueda H (2011) A new frontier of amino acid fermentation: metabolic pathway design and advanced fermentation technology. International Union of Microbiological Societies 2011 Congress (IUMS 2011 Congress), Sapporo, Japan.

5. Kinoshita S, Udaka S, Shimono M (1957) Studies on the amino acid fermentation. J Gen Appl Microbiol 3: 193-205.

6. Kramer R (1996) Genetic and physiological approaches for the production of amino acids. Journal of Biotechnology 45: 1-21.

7. Ikeda M, Ohnishi J, Hayashi M, Mitsuhashi S (2006) A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production. J Ind Microbiol Biotechnol 33: 610-615.

8. Vrljic M, Sahm H, Eggeling L (1996) A new type of transporter with a new type of a cellular function: L-lysine export from Corynebacterium glutamicum. Mol Microbiol 22: 815-826.

9. Hori H, Yoneyama H, Tobe R, Ando T, Isogai E, et al. (2011) Inducible L-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli. Appl Environ Microbiol 77: 4027-4034.

Seryoung and Yoneyama, J Biotechnol Biomater 2013, 3:1 DOI: 10.4172/2155-952X.1000e118

Kim Seryoung and Hiroshi Yoneyama*

Citation: Seryoung K, Yoneyama H (2013) Amino Acid Exporter: A Tool for the Next-Generation Microbial Fermentation. J Biotechnol Biomater 3: e118. doi:10.4172/2155-952X.1000e118

Copyright: © 2013 Seryoung K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

In this context, the molecular mechanism of amino acids export has long been unknown until the lysE gene was identified to encode L-lysine exporter, LysE, in C. glutamicum [8]. Interestingly, LysE also exports L-arginine. After this prominent work, more than ten membraneproteins have appeared to export amino acids and their analogues in C.glutamicum and Escherichia coli, substrates of which are L-isoleucine,L-glutamic acid, L-threonine, L-cysteine, L-leucine, L-valine, andL-aromatic amino acids. In addition to these exporters, L-alanineexporter AlaE (formerly YgaW) has recently been identified in E. coli[9]. The existence of amino acid exporters raises an important questionof why bacterial cells possess these transporters to export L-amino acids

Amino acid fermentation was triggered in 1957 by the discovery of the soil bacterium, Corynebacterium glutamicum, which produces large amounts of glutamic acid in culture medium [5]. Since then, efforts to produce various amino acids by microbial fermentation resulted in the development of cost-effective strains with extremely high productivity. The early strategies for obtaining such a high producer strain were based on mutagenesis and screening, called metabolic engineering, which lead to changes in metabolic flow toward a certain amino acid of interest mainly by deregulation of the amino acid biosynthetic pathway [6]. As a next step, genetic engineering has been employed recombinant DNA techniques to improve productivity by cloning a gene that encodes a rate-limiting enzyme along the biosynthetic pathway of the amino acid, or by introducing beneficial mutant alleles into the chromosome of a wild-type background strain [7].

at the expense of energy, despite the facts that they are anabolic, but not catabolic, primary metabolites and also are important building blocks of proteins. The answer to this question will be obtained through in-depth understanding of the molecular mechanism of substrate excretion by these exporters and of their regulation. Furthermore, studies on the novel aspects of amino acid metabolism, that is export, will pave the way for the next generation amino acid fermentation technology.

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ISSN: 2155-952X

Journal of Biotechnology & Biomaterials