title: Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a mechanosensitive channel homolog, induce L-glutamic acid production.
abstract: Corynebacterium glutamicum is a biotin auxotroph that secretes L-glutamic acid in response to biotin limitation; this process is employed in industrial L-glutamic acid production. Fatty acid ester surfactants and penicillin also induce L-glutamic acid secretion, even in the presence of biotin. However, the mechanism of L-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in L-glutamic acid secretion without induction. In this study, we analyzed odhA disruptants and found that those which exhibited constitutive L-glutamic acid secretion carried additional mutations in the NCgl1221 gene, which encodes a mechanosensitive channel homolog. These NCgl1221 gene mutations lead to constitutive L-glutamic acid secretion even in the absence of odhA disruption and also render cells resistant to an L-glutamic acid analog, 4-fluoroglutamic acid. Disruption of the NCgl1221 gene essentially abolishes L-glutamic acid secretion, causing an increase in the intracellular L-glutamic acid pool under biotin-limiting conditions, while amplification of the wild-type NCgl1221 gene increased L-glutamate secretion, although only in response to induction. These results suggest that the NCgl1221 gene encodes an L-glutamic acid exporter. We propose that treatments that induce L-glutamic acid secretion alter membrane tension and trigger a structural transformation of the NCgl1221 protein, enabling it to export L-glutamic acid.
authors.affiliation: Fermentation & Biotechnology Laboratories, Ajinomoto Co., Suzuki-cho, Kawasaki, Kanagawa 210-8681, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Seiko
authors.initials: S
authors.lastname: Hirano
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Masaaki
authors.initials: M
authors.lastname: Wachi
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D048230:Corynebacterium glutamicum / Q000187:drug effects / Q000235:genetics*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008958:Models, Molecular; D016254:Mutagenesis, Insertional; D009154:Mutation
chemical_list: D026905:Amino Acid Transport Systems; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005971:Glutamates; C038473:4-fluoroglutamic acid; D018698:Glutamic Acid