Systems pathway engineering of Corynebacterium crenatum for improved L-arginine production

Sci Rep. 2016 Jun 24:6:28629. doi: 10.1038/srep28629.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism*
  • Bacterial Proteins / metabolism*
  • Biosynthetic Pathways / physiology*
  • Corynebacterium / metabolism*
  • Corynebacterium / physiology*
  • Fermentation / physiology
  • Gene Expression Regulation, Bacterial / physiology
  • Glucose / metabolism
  • Ketoglutaric Acids / metabolism
  • Metabolic Engineering / methods
  • NADP / metabolism
  • Pentose Phosphate Pathway / physiology

Substances

  • Bacterial Proteins
  • Ketoglutaric Acids
  • NADP
  • Arginine
  • Glucose