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  • Title: Characterization and engineering of the Lrp/AsnC family regulator SACE_5717 for erythromycin overproduction in Saccharopolyspora erythraea.
    Author: Liu J, Chen Y, Li L, Yang E, Wang Y, Wu H, Zhang L, Wang W, Zhang B.
    Journal: J Ind Microbiol Biotechnol; 2019 Jul; 46(7):1013-1024. PubMed ID: 31016583.
    Abstract:
    In this work, we found that the Lrp/AsnC family protein SACE_5717 negatively regulated erythromycin biosynthesis in S. erythraea. Disruption of SACE_5717 led to a 27% improvement in the yield of erythromycin in S. erythraea A226. SACE_5717 directly repressed its own gene expression, as well as that of the adjacent gene SACE_5716 by binding to the target sequence 5'-GAACGTTCGCCGTCACGCC-3'. The predicted LysE superfamily protein SACE_5716 directly influenced the export of lysine, histidine, threonine and glycine in S. erythraea. Arginine, tyrosine and tryptophan were characterized as the effectors of SACE_5717 by weakening the binding affinity of SACE_5717. In the industrial S. erythraea WB strain, deletion of SACE_5717 (WBΔSACE_5717) increased erythromycin yield by 20%, and by 36% when SACE_5716 was overexpressed in WBΔSACE_5717 (WBΔSACE_5717/5716). In large-scale 5-L fermentation experiment, erythromycin yield in the engineered strain WBΔSACE_5717/5716 reached 4686 mg/L, a 41% enhancement over 3323 mg/L of the parent WB strain.
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