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

Scientific Reports
2016.0

Abstract

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Corynebacterium crenatum</jats:italic> (subspecies of <jats:italic>Corynebacterium glutamicum</jats:italic>) through screening and mutation breeding. In this work, we performed systems pathway engineering of <jats:italic>C. crenatum</jats:italic> 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<jats:sup>−1</jats:sup> L-arginine with yield up to 0.431 g L-arginine g<jats:sup>−1</jats:sup> glucose in fed-batch fermentation.

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