Deletions of conserved extracytoplasmic function sigma factors-encoding genes in Streptomyces have a major impact on secondary metabolism

Olga N Sekurova, Martin Zehl, Michael Predl, Peter Hunyadi, Thomas Rattei, Sergey B Zotchev (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

BACKGROUND: Ethanol shock significantly affects expression of over 1200 genes in Streptomyces venezuelae NRRL B-65,442, including those involved in secondary metabolite biosynthesis and a cryptic gene pepX, which encodes a 19-amino acid peptide with an unknown function.

RESULTS: To establish a possible correlation between the PepX peptide and secondary metabolism in S. venezuelae, its gene was deleted, followed by analyses of the transcriptome and secondary metabolome of the mutant. Although the secondary metabolome of the pepX mutant was not strongly affected, pepX deletion, similar to ethanol shock, mostly resulted in downregulated expression of secondary metabolite biosynthesis gene clusters (BGCs). At the same time, there was a reverse correlation between the expression of certain extracytoplasmic function sigma factors (ECFs) and several BGCs. Individual deletions of three selected ECF-coding genes conserved in Streptomyces that were upregulated upon both pepX deletion and ethanol shock, had a profound positive effect on the expression of BGCs, which also correlated with the overproduction of specific secondary metabolites. Deletion of one such ECF-coding gene in a marine sponge-derived Streptomyces sp. also significantly altered the secondary metabolite profile, suggesting an important role of this ECF in the regulation of secondary metabolism.

CONCLUSIONS: These findings pave the way for the activation or upregulation of BGCs in Streptomyces bacteria harboring genes for ECFs homologous to those identified in this study, hereby assisting in the discovery of novel bioactive secondary metabolites.

Original languageEnglish
Article number201
Pages (from-to)201
JournalMicrobial Cell Factories
Volume23
Issue number1
DOIs
Publication statusPublished - 18 Jul 2024

Austrian Fields of Science 2012

  • 106013 Genetics
  • 104013 Natural product chemistry
  • 106022 Microbiology

Keywords

  • Streptomyces/genetics
  • Secondary Metabolism/genetics
  • Sigma Factor/genetics
  • Gene Expression Regulation, Bacterial
  • Gene Deletion
  • Multigene Family
  • Bacterial Proteins/genetics
  • Ethanol/metabolism
  • Transcriptome
  • Streptomyces bacteria
  • Extracytoplasmic function sigma factors
  • Transcriptomics
  • Secondary metabolism

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