Ikeda Masato, Ohnishi Junko, Hayashi Mikiro, Mitsuhashi Satoshi
Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Minami-minowa, 399-4598, Nagano, Japan.
J Ind Microbiol Biotechnol. 2006 Jul;33(7):610-5. doi: 10.1007/s10295-006-0104-5. Epub 2006 Feb 28.
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.
基于基因组学的进展，我们开发了一种新方法，该方法利用基因组信息来培育高效的氨基酸生产者。对一种工业L-赖氨酸生产菌株及其天然祖先进行比较基因组分析，确定了与L-赖氨酸生物合成相关的基因中的多种突变。在这些突变中，我们确定了相关终端途径中的两个突变是L-赖氨酸生产的关键突变，以及中心代谢中的三个突变导致了产量增加。当这五个突变组合在野生型基因组中时，生产速率和最终L-赖氨酸产量都显著提高。进一步结合转录组分析的研究表明，还需要其他尚未确定的突变来支持原始生产菌株所观察到的L-赖氨酸产量。在这里，我们描述了我们的菌株重建方法的要点，并讨论了通过将基因组学与经典菌株改良相结合而揭示的L-赖氨酸高产机制。
