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Co-expression of a pair of interdependent regulators coding genes ovmZ and ovmW awakens the production of angucyclinones antibiotics in Streptomyces neyagawaensis. | LitMetric

AI Article Synopsis

  • Researchers discovered that activating specific gene clusters (BGCs) in streptomycetes can lead to the production of new compounds, revealing many silent biosynthetic potential.* -
  • The study identified that two related genes, ovmZ and ovmW, are crucial for activating these silent BGCs, allowing the production of compounds like gephyromycin A when both genes are overexpressed in Streptomyces neyagawaensis.* -
  • The findings suggest that co-overexpression of ovmZ and ovmW could be a promising method for stimulating the production of secondary metabolites across various actinobacteria.*

Article Abstract

Background: Microbial genome sequencing and analysis revealed the presence of abundant silent secondary metabolites biosynthetic gene clusters (BGCs) in streptomycetes. Activating these BGCs has great significance for discovering new compounds and novel biosynthetic pathways.

Results: In this study, we found that ovmZ and ovmW homologs, a pair of interdependent transcriptional regulators coding genes, are widespread in actinobacteria and closely associated with the biosynthesis of secondary metabolites. Through co-overexpression of native ovmZ and ovmW in Streptomyces neyagawaensis NRRL B-3092, a silent type II polyketide synthase (PKS) gene cluster was activated to produce gephyromycin A, tetrangomycin and fridamycin E with the yields of 22.3 ± 8.0 mg/L, 4.8 ± 0.5 mg/L and 20.3 ± 4.1 mg/L respectively in the recombinant strain of S.ne/pZW. However, expression of either ovmZ or ovmW failed to activate this gene cluster. Interestingly, overexpression of the heterologous ovmZ and ovmW pair from oviedomycin BGC of S. ansochromogenes 7100 also led to awakening of this silent angucyclinone BGC in S. neyagawaensis.

Conclusion: A silent angucyclinone BGC was activated by overexpressing both ovmZ and ovmW in S. neyagawaensis. Due to the wide distribution of ovmZ and ovmW in the BGCs of actinobacteria, co-overexpression of ovmZ and ovmW could be a strategy for activating silent BGCs, thus stimulating the biosynthesis of secondary metabolites.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264864PMC
http://dx.doi.org/10.1186/s12934-024-02478-yDOI Listing

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