Bilyk, B, Kim, S, Fazal, A et al. (2 more authors) (2020) Regulation of Antimycin Biosynthesis Is Controlled by the ClpXP Protease. mSphere, 5 (2). e00144-20. ISSN 2379-5042
Abstract
The survival of any microbe relies on its ability to respond to environmental change. Use of extracytoplasmic function (ECF) RNA polymerase sigma (σ) factors is a major strategy enabling dynamic responses to extracellular signals. Streptomyces species harbor a large number of ECF σ factors, nearly all of which are uncharacterized, but those that have been characterized generally regulate genes required for morphological differentiation and/or response to environmental stress, except for σAntA, which regulates starter-unit biosynthesis in the production of antimycin, an anticancer compound. Unlike a canonical ECF σ factor, whose activity is regulated by a cognate anti-σ factor, σAntA is an orphan, raising intriguing questions about how its activity may be controlled. Here, we reconstituted in vitro ClpXP proteolysis of σAntA but not of a variant lacking a C-terminal di-alanine motif. Furthermore, we show that the abundance of σAntA in vivo was enhanced by removal of the ClpXP recognition sequence and that levels of the protein rose when cellular ClpXP protease activity was abolished. These data establish direct proteolysis as an alternative and, thus far, unique control strategy for an ECF RNA polymerase σ factor and expands the paradigmatic understanding of microbial signal transduction regulation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Bilyk et al. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | ClpXP, ECF sigma factors, Streptomyces, antimycin, proteolysis, regulation of secondary metabolism |
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 BBSRC (Biotechnology & Biological Sciences Research Council) BB/N007980/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Mar 2020 16:39 |
Last Modified: | 22 Apr 2020 14:06 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/mSphere.00144-20 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158709 |