title: Systems pathway engineering of Corynebacterium crenatum for improved L-arginine production.
abstract: L-arginine is an important amino acid in food and pharmaceutical industries. Until now, the main production method of L-arginine in China is the highly polluting keratin acid hydrolysis. The industrial level L-arginine production by microbial fermentation has become an important task. In previous work, we obtained a new L-arginine producing Corynebacterium crenatum (subspecies of Corynebacterium glutamicum) through screening and mutation breeding. In this work, we performed systems pathway engineering of C. crenatum for improved L-arginine production, involving amplification of L-arginine biosynthetic pathway flux by removal of feedback inhibition and overexpression of arginine operon; optimization of NADPH supply by modulation of metabolic flux distribution between glycolysis and pentose phosphate pathway; increasing glucose consumption by strengthening the preexisting glucose transporter and exploitation of new glucose uptake system; channeling excess carbon flux from glycolysis into tricarboxylic acid cycle to alleviate the glucose overflow metabolism; redistribution of carbon flux at α-ketoglutarate metabolic node to channel more flux into L-arginine biosynthetic pathway; minimization of carbon and cofactor loss by attenuation of byproducts formation. The final strain could produce 87.3 g L(-1) L-arginine with yield up to 0.431 g L-arginine g(-1) glucose in fed-batch fermentation.
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zaiwei
authors.initials: Z
authors.lastname: Man
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.|State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Rao
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Taowei
authors.initials: T
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Xu
mesh_terms: D001120:Arginine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000502:physiology*; D003352:Corynebacterium / Q000378:metabolism* / Q000502:physiology*; D005285:Fermentation / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods; D009249:NADP / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D007656:Ketoglutaric Acids; D009249:NADP; D001120:Arginine; D005947:Glucose