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Improvement of the Enediyne Antitumor Antibiotic C-1027 Production by Manipulating Its Biosynthetic Pathway Regulation in Streptomyces globisporus

  作者 Chen, YH; Yin, M; Horsman, GP; Shen, B  
  选自 期刊  Journal of natural products;  卷期  2011年74-3;  页码  420-424  
  关联知识点  
 

[摘要]The production of C-1027 in Streptomyces globisporus was previously increased 2- to 3-fold by manipulating three pathway-specific activators, SgcR1, SgcR2, and SgcR3. In this study, we have further characterized two putative C-1027 regulatory genes, sgcE1 and sgcR, by in vivo inactivation. The HxlR family DNA-binding protein SgcE1 was not essential for C-1027 biosynthesis, since inactivation of sgcE1 showed no effect on C-1027 production. In contrast, the proposed repressive role of the sgcR gene was confirmed by a 3-fold increase in C-1027 production in the Delta sgcR mutant S. globisporus SB1022 strain relative to the wild-type strain. Considering SgcR shows no significant similarity to any protein of known function, it may be representative of a new family of regulatory proteins. Finally, overexpression of the previously characterized activator sgcR1 in S. globisporus SB1022 increased the C-1027 yield to 37.5 +/- 7.7 mg/L, which is about 7-fold higher than the wild-type strain.

 
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