Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σAntA
- Published
- Accepted
- Subject Areas
- Biochemistry, Biotechnology, Microbiology, Molecular Biology
- Keywords
- Streptomyces, antibiotics, secondary metabolites, actinomycetes, gene regulation, ECF sigma factor, antimycin
- Copyright
- © 2014 Seipke et al.
- Licence
- 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.
- Cite this article
- 2014. Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σAntA. PeerJ PrePrints 2:e203v1 https://doi.org/10.7287/peerj.preprints.203v1
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 σAntA which represents a new sub-family of ECF σ factors that is only found in antimycin producing strains. We show that σAntA controls production of the unusual precursor 3-aminosalicylate which is absolutely required for the production of antimycins. σAntA is highly conserved in antimycin producing strains and the -10 and -35 elements at the σAntA 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 σAntA 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.
Supplemental Information
Supplementary Information
This document contains two supplementary tables and four supplementary figures as well as legends for each of these.