title: Branched-Chain Amino Acids.
abstract: Branched-chain amino acids (BCAAs), viz., L-isoleucine, L-leucine, and L-valine, are essential amino acids that cannot be synthesized in higher organisms and are important nutrition for humans as well as livestock. They are also valued as synthetic intermediates for pharmaceuticals. Therefore, the demand for BCAAs in the feed and pharmaceutical industries is increasing continuously. Traditional industrial fermentative production of BCAAs was performed using microorganisms isolated by random mutagenesis. A collection of these classical strains was also scientifically useful to clarify the details of the BCAA biosynthetic pathways, which are tightly regulated by feedback inhibition and transcriptional attenuation. Based on this understanding of the metabolism of BCAAs, it is now possible for us to pursue strains with higher BCAA productivity using rational design and advanced molecular biology techniques. Additionally, systems biology approaches using augmented omics information help us to optimize carbon flux toward BCAA production. Here, we describe the biosynthetic pathways of BCAAs and their regulation and then overview the microorganisms developed for BCAA production. Other chemicals, including isobutanol, i.e., a second-generation biofuel, can be synthesized by branching the BCAA biosynthetic pathways, which are also outlined.
authors.affiliation: Green Earth Institute Co., Ltd, Hongo, Tokyo, Japan.|Green Earth Research Center, Kisarazu, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Green Earth Institute Co., Ltd, Hongo, Tokyo, Japan.|Green Earth Research Center, Kisarazu, Chiba, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Tsuchisaka
authors.affiliation: Green Earth Institute Co., Ltd, Hongo, Tokyo, Japan. info-green@gei.co.jp.|Green Earth Research Center, Kisarazu, Chiba, Japan. info-green@gei.co.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yukawa
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis* / Q000235:genetics; D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis* / Q000235:genetics*; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000502:physiology; D001688:Biological Products / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology*; D005285:Fermentation / Q000502:physiology; D024861:Genetic Enhancement / Q000379:methods; D060847:Metabolic Engineering / Q000379:methods*
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; D001688:Biological Products
keywords: Branched-chain amino acids (BCAAs); Corynebacterium glutamicum; Escherichia coli; Feedback inhibition; Isobutanol; L-Isoleucine; L-Leucine; L-Valine; Metabolic engineering; Transcriptional attenuation