Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ (AntA.)

Seipke, Ryan F., Patrick, Elaine and Hutchings, Matthew I. (2014) Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ (AntA.). PeerJ, 2. ISSN 2167-8359

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Abstract

Antimycins are an extended family of depsipeptides that are made by filamentous actinomycete bacteria and were first isolated more than 60 years ago. Recently, antimycins have attracted renewed interest because of their activities against the anti-apoptotic machineries inside human cells which could make them promising anti-cancer compounds. The biosynthetic pathway for antimycins was recently characterised but very little is known about the organisation and regulation of the antimycin (ant) gene cluster. Here we report that the ant gene cluster in Streptomyces albus is organized into four transcriptional units; the antBA, antCDE, antGF and antHIJKLMNO operons. Unusually for secondary metabolite clusters, the antG and antH promoters are regulated by an extracytoplasmic function (ECF) RNA polymerase sigma factor named σ (AntA) which represents a new sub-family of ECF σ factors that is only found in antimycin producing strains. We show that σ (AntA) controls production of the unusual precursor 3-aminosalicylate which is absolutely required for the production of antimycins. σ (AntA) is highly conserved in antimycin producing strains and the -10 and -35 elements at the σ (AntA) regulated antG and antH promoters are also highly conserved suggesting a common mechanism of regulation. We also demonstrate that altering the C-terminal Ala-Ala residues found in all σ (AntA) proteins to Asp-Asp increases expression of the antFG and antGHIJKLMNO operons and we speculate that this Ala-Ala motif may be a signal for the protease ClpXP.

Item Type: Article
Additional Information: © 2014 Seipke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science
Depositing User: Pure Connector
Date Deposited: 09 Jul 2014 12:24
Last Modified: 21 Apr 2020 23:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/48988
DOI: 10.7717/peerj.253

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