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J Ind Microbiol Biotechnol. 2006 Jul;33(7):610-5. Epub 2006 Feb 28.

A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production.

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  • 1Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Minami-minowa, 399-4598, Nagano, Japan. m_ikeda@shinshu-u.ac.jp


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.

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