title: A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production.
abstract: Based on the progress in genomics, we have developed a novel approach that employs genomic information to generate an efficient amino acid producer. A comparative genomic analysis of an industrial L-lysine producer with its natural ancestor identified a variety of mutations in genes associated with L-lysine biosynthesis. Among these mutations, we identified two mutations in the relevant terminal pathways as key mutations for L-lysine production, and three mutations in central metabolism that resulted in increased titers. These five mutations when assembled in the wild-type genome led to a significant increase in both the rate of production and final L-lysine titer. Further investigations incorporated with transcriptome analysis suggested that other as yet unidentified mutations are necessary to support the L-lysine titers observed by the original production strain. Here we describe the essence of our approach for strain reconstruction, and also discuss mechanisms of L-lysine hyperproduction unraveled by combining genomics with classical strain improvement.
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Minami-minowa, 399-4598, Nagano, Japan. m_ikeda@shinshu-u.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Ikeda
authors.forename: Junko
authors.initials: J
authors.lastname: Ohnishi
authors.forename: Mikiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mitsuhashi
mesh_terms: D048230:Corynebacterium glutamicum / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005818:Genetic Engineering; D016680:Genome, Bacterial / Q000235:genetics*; D007218:Industrial Microbiology / Q000379:methods*; D008239:Lysine / Q000096:biosynthesis* / Q000235:genetics; D016296:Mutagenesis; D009154:Mutation
chemical_list: D008239:Lysine