Coordinate regulation of antimycin and candicidin biosynthesis

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McLean, Thomas C. and Hoskisson, Paul A. and Seipke, Ryan F. (2016) Coordinate regulation of antimycin and candicidin biosynthesis. mSphere, 1 (6). pp. 1-35. ISSN 2379-5042

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Abstract

Streptomyces species produce an incredible array of high-value specialty chemicals and medicinal therapeutics. A single species typically harbors ~30 biosynthetic pathways, but only a mere handful of them are expressed in the laboratory, thus poor understanding of how natural products biosynthesis is regulated is a major bottleneck in drug discovery. Antimycins are a large family of anticancer compounds widely produced by Streptomyces species and their regulation is atypical compared to that of most other natural products. Here we demonstrate that antimycin production by Streptomyces albus S4 is regulated by FscRI, a PAS-LuxR-family cluster-situated regulator of the polyene antifungal agent, candicidin. We report that heterologous production of antimycins by Streptomyces coelicolor is dependent on FscRI and show that FscRI activates transcription of key biosynthetic genes. We also demonstrate through ChIP sequencing that FscRI regulation is direct and we provide evidence to suggest that this regulation strategy is conserved and unique to short form antimycin gene clusters. Our study provides direct in vivo evidence for cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products and expands the paradigmatic understanding of the regulation of secondary metabolism.

ORCID iDs

McLean, Thomas C., Hoskisson, Paul A. ORCID logoORCID: https://orcid.org/0000-0003-4332-1640 and Seipke, Ryan F.;
  • Item type:Article
    ID code:58752
    Dates:
    Date
    Event
    7 December 2016
    Published
    11 November 2016
    Accepted
    10 October 2016
    Submitted
    Notes:© 2016 McLean et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license . McLean TC, Hoskisson PA, Seipke RF. 2016. Coordinate Regulation of Antimycin and Candicidin Biosynthesis. mSphere 1:10.1128/msphere.00305-16. https://doi.org/10.1128/msphere.00305-16
    Subjects:Medicine > Therapeutics. Pharmacology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:21 Nov 2016 10:45
    Last modified:11 Nov 2024 11:34
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/58752
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