Inactivation of the positive LuxR-type oligomycin biosynthesis regulators OlmRI and OlmRII increases avermectin production in Streptomyces avermitilis

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• 作者：Qing Yu (1)
  LinQuan Bai (1)
  XiuFen Zhou (1)
  ZiXin Deng (1)
  
• 关键词：Streptomyces ; oligomycin ; regulation ; avermectin ; enhanced production
• 刊名：Chinese Science Bulletin
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：57
• 期：8
• 页码：869-876
• 全文大小：845KB
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• 作者单位：Qing Yu (1)
  LinQuan Bai (1)
  XiuFen Zhou (1)
  ZiXin Deng (1)
  
  1. State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, China
  
• ISSN：1861-9541

文摘

Oligomycins are a group of 26 macrocyclic lactones that exhibit broad biological activities, including antifungal, anticancer and nematocidal activities. Analysis of the oligomycin biosynthetic gene cluster (olm) in S. avermitilis revealed 2 tandem LuxR-type regulators, OlmRI (931 aa) and OlmRII (941 aa), with shared identity of 38%. Gene replacement of olmRI or olmRII abolished oligomycin production, and this production could be partially restored in the disruptants by introducing cloned olmRI and olmRII with their native promoters, demonstrating the essential role of OlmRI and OlmRII for oligomycin biosynthesis. Quantitative real-time RT-PCR analysis revealed that transcription of 14 olm genes was differentially affected by the deletion of olmRI and olmRII. Unexpectedly, avermectin production in both mutants was enhanced at least 4-fold. The identification of the positive cluster-situated regulators, OlmRI and OlmRII, paves the way for the transcriptional analysis of oligomycin biosynthesis and for the enhancement of oligomycin and avermectin production through regulator engineering.