McLean, TC, Hoskisson, PA and Seipke, RF orcid.org/0000-0002-6156-8498 (2016) Coordinate regulation of antimycin and candicidin biosynthesis. mSphere, 1 (6). e00305-16. ISSN 2379-5042
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2016 McLean et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Supplemental Material is distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number British Soc Antimicrobial Chemotherapy GA20104_006P BBSRC BB/N007980/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Nov 2016 10:17 |
Last Modified: | 10 Oct 2017 10:54 |
Published Version: | https://doi.org/10.1128/mSphere.00305-16 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/mSphere.00305-16 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107429 |