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  • Title: [Highly efficient production of L-valine by multiplex metabolic engineering of Corynebacterium glutamicum].
    Author: Zhao K, Cheng J, Guo L, Gao C, Song W, Wu J, Liu J, Liu Y, Liu L, Chen X.
    Journal: Sheng Wu Gong Cheng Xue Bao; 2023 Aug 25; 39(8):3253-3272. PubMed ID: 37622359.
    Abstract:
    As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
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