Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Japan
Received date: February 27, 2013; Accepted date: February 28, 2013; Published date: March 05, 2013
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.
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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 . 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 .
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 . 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 . 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 .
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 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. 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.
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 . Interestingly, LysE also exports L-arginine. After 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 . The existence of amino acid exporters raises an important question of why bacterial cells possess these transporters to export L-amino acids 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.