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

• Published in: Journal of industrial microbiology & biotechnology 2006-07, Vol.33 (7), p.610-615
• Main Authors: IKEDA, Masato, OHNISHI, Junko, HAYASHI, Mikiro, MITSUHASHI, Satoshi
• Format: Article
• Language: English
• Subjects: Amino acids; Biological and medical sciences; Biosynthesis; Biotechnology; Corynebacterium glutamicum; Corynebacterium glutamicum - genetics; Corynebacterium glutamicum - metabolism; DNA Mutational Analysis; Fundamental and applied biological sciences. Psychology; Genetic Engineering; Genome, Bacterial - genetics; Genomes; Genomics; Industrial Microbiology - methods; Lysine - biosynthesis; Lysine - genetics; Mutagenesis; Mutation
• ISSN: 1367-5435; 1476-5535
• DOI: 10.1007/s10295-006-0104-5

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.