The σ54 system directly regulates bacterial natural product genes

Abstract Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutics and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery controlling their transcription. Recent findings suggest that t...

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Autores principales:	Muqing Ma, Roy D. Welch, Anthony G. Garza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e8349d92f1ef40f8a46f119ddb48ef11
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spelling	oai:doaj.org-article:e8349d92f1ef40f8a46f119ddb48ef112021-12-02T15:52:59ZThe σ54 system directly regulates bacterial natural product genes10.1038/s41598-021-84057-42045-2322https://doaj.org/article/e8349d92f1ef40f8a46f119ddb48ef112021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84057-4https://doaj.org/toc/2045-2322Abstract Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutics and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery controlling their transcription. Recent findings suggest that the σ54 system, which includes σ54-loaded RNA polymerase and transcriptional activators called enhancer binding proteins (EBPs), might be a common regulator of natural product genes. Here, we explored this idea by analyzing a selected group of putative σ54 promoters identified in Myxococcus xanthus natural product gene clusters. We show that mutations in putative σ54-RNA polymerase binding regions and in putative Nla28 EBP binding sites dramatically reduce in vivo promoter activities in growing and developing cells. We also show in vivo promoter activities are reduced in a nla28 mutant, that Nla28 binds to wild-type fragments of these promoters in vitro, and that in vitro binding is lost when the Nla28 binding sites are mutated. Together, our results indicate that M. xanthus uses σ54 promoters for transcription of at least some of its natural product genes. Interestingly, the vast majority of experimentally confirmed and putative σ54 promoters in M. xanthus natural product loci are located within genes and not in intergenic sequences.Muqing MaRoy D. WelchAnthony G. GarzaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muqing Ma Roy D. Welch Anthony G. Garza The σ54 system directly regulates bacterial natural product genes
description	Abstract Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutics and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery controlling their transcription. Recent findings suggest that the σ54 system, which includes σ54-loaded RNA polymerase and transcriptional activators called enhancer binding proteins (EBPs), might be a common regulator of natural product genes. Here, we explored this idea by analyzing a selected group of putative σ54 promoters identified in Myxococcus xanthus natural product gene clusters. We show that mutations in putative σ54-RNA polymerase binding regions and in putative Nla28 EBP binding sites dramatically reduce in vivo promoter activities in growing and developing cells. We also show in vivo promoter activities are reduced in a nla28 mutant, that Nla28 binds to wild-type fragments of these promoters in vitro, and that in vitro binding is lost when the Nla28 binding sites are mutated. Together, our results indicate that M. xanthus uses σ54 promoters for transcription of at least some of its natural product genes. Interestingly, the vast majority of experimentally confirmed and putative σ54 promoters in M. xanthus natural product loci are located within genes and not in intergenic sequences.
format	article
author	Muqing Ma Roy D. Welch Anthony G. Garza
author_facet	Muqing Ma Roy D. Welch Anthony G. Garza
author_sort	Muqing Ma
title	The σ54 system directly regulates bacterial natural product genes
title_short	The σ54 system directly regulates bacterial natural product genes
title_full	The σ54 system directly regulates bacterial natural product genes
title_fullStr	The σ54 system directly regulates bacterial natural product genes
title_full_unstemmed	The σ54 system directly regulates bacterial natural product genes
title_sort	σ54 system directly regulates bacterial natural product genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e8349d92f1ef40f8a46f119ddb48ef11
work_keys_str_mv	AT muqingma thes54systemdirectlyregulatesbacterialnaturalproductgenes AT roydwelch thes54systemdirectlyregulatesbacterialnaturalproductgenes AT anthonyggarza thes54systemdirectlyregulatesbacterialnaturalproductgenes AT muqingma s54systemdirectlyregulatesbacterialnaturalproductgenes AT roydwelch s54systemdirectlyregulatesbacterialnaturalproductgenes AT anthonyggarza s54systemdirectlyregulatesbacterialnaturalproductgenes
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The σ54 system directly regulates bacterial natural product genes

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