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

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...

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Autores principales: Seipke, Ryan F., Patrick, Elaine, Hutchings, Matthew I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933326/
https://www.ncbi.nlm.nih.gov/pubmed/24688837
http://dx.doi.org/10.7717/peerj.253
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author Seipke, Ryan F.
Patrick, Elaine
Hutchings, Matthew I.
author_facet Seipke, Ryan F.
Patrick, Elaine
Hutchings, Matthew I.
author_sort Seipke, Ryan F.
collection PubMed
description 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.
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spelling pubmed-39333262014-03-31 Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA) Seipke, Ryan F. Patrick, Elaine Hutchings, Matthew I. PeerJ Biochemistry 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. PeerJ Inc. 2014-02-06 /pmc/articles/PMC3933326/ /pubmed/24688837 http://dx.doi.org/10.7717/peerj.253 Text en © 2014 Seipke et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Biochemistry
Seipke, Ryan F.
Patrick, Elaine
Hutchings, Matthew I.
Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title_full Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title_fullStr Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title_full_unstemmed Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title_short Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σ(AntA)
title_sort regulation of antimycin biosynthesis by the orphan ecf rna polymerase sigma factor σ(anta)
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933326/
https://www.ncbi.nlm.nih.gov/pubmed/24688837
http://dx.doi.org/10.7717/peerj.253
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