Ning Li, Sha Xu, G. Du
Sep 15, 2020
Citations
2
Influential Citations
16
Citations
Journal
Biochemical Engineering Journal
Abstract
Abstract L-Homoserine is a platform chemical used for the production of l -methionine and other valuable compounds. In this study, we constructed an initial l -homoserine-producing strain by metabolic engineering of Corynebacterium glutamicum ATCC 13032, including deletion of thrB, mcbR, and metD and overexpression of lysC, asd, and hom, resulting in a strain capable of producing 1.2 g/L l -homoserine and 4.8 g/L l -lysine. The metabolic flux of l -homoserine was further enhanced by overexpressing feedback-insensitive pyruvate carboxylase (encoded by pyc) from C. glutamicum ATCC 13032 and l -aspartate aminotransferase (encoded by aspC) from E. coli in order to increase oxaloacetate and l -aspartate supplies. Additionally, overexpression of brnFE, which encodes the two-component export system, improved l -homoserine production by 2-fold, suggesting involvement of the brnFE operon in l -homoserine export. Moreover, attenuated expression of dapA and icd downregulated l -lysine biosynthesis and the TCA cycle, resulting in a 25.9 % increase in l -homoserine production (up to 3.4 g/L). Furthermore, overexpression of lysCT311I, asd from C. glutamicum ATCC 13032, and the thrAS345F from E. coli K12-MG1655 resulted in l -homoserine production of 8.8 g/L and demonstrated C. glutamicum as having great potential for industrial production of l- homoserine and l -methionine.