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.