title: (L)-Valine production with minimization of by-products' synthesis in Corynebacterium glutamicum and Brevibacterium flavum.
abstract: Corynebacterium glutamicum ATCC13032 and Brevibacterium flavum JV16 were engineered for L-valine production by over-expressing ilvEBN ( r ) C genes at 31 °C in 72 h fermentation. Different strategies were carried out to reduce the by-products' accumulation in L-valine fermentation and also to increase the availability of precursor for L-valine biosynthesis. The native promoter of ilvA of C. glutamicum was replaced with a weak promoter MPilvA (P-ilvAM1CG) to reduce the biosynthetic rate of L-isoleucine. Effect of different relative dissolved oxygen on L-valine production and by-products' formation was recorded, indicating that 15 % saturation may be the most appropriate relative dissolved oxygen for L-valine fermentation with almost no L-lactic acid and L-glutamate formed. To minimize L-alanine accumulation, alaT and/or avtA was inactivated in C. glutamicum and B. flavum, respectively. Compared to high concentration of L-alanine accumulated by alaT inactivated strains harboring ilvEBN ( r ) C genes, L-alanine concentration was reduced to 0.18 g/L by C. glutamicum ATCC13032MPilvA△avtA pDXW-8-ilvEBN ( r ) C, and 0.22 g/L by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. Meanwhile, L-valine production and conversion efficiency were enhanced to 31.15 g/L and 0.173 g/g by C. glutamicum ATCC13032MPilvA△avtA pDXW-8-ilvEBN ( r ) C, 38.82 g/L and 0.252 g/g by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. This study provides combined strategies to improve L-valine yield by minimization of by-products' production.
authors.affiliation: Laboratory of Renewable Energy and Gas Hydrate, Chinese Academy of Sciences, Guangzhou, 510640, People's Republic of China. houxiaohu828@163.com
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Hou
authors.forename: Xinde
authors.initials: X
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Qian
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
mesh_terms: D040142:Brevibacterium flavum / Q000737:chemistry / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000737:chemistry / Q000378:metabolism*; D005285:Fermentation; D010100:Oxygen / Q000378:metabolism; D014633:Valine / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014633:Valine; D010100:Oxygen