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Related Experiment Video

Updated: Apr 24, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
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Modulating Complex Secondary Metabolism in Streptomyces rimosus by Targeted Genome Engineering.

Martina Avbelj1, Lucija Slemc1, Alen Pšeničnik1

  • 1Food Science and Technology Department, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia.

Food Technology and Biotechnology
|April 23, 2026
PubMed
Summary

Many microbial biosynthetic gene clusters (BGCs) are silent, but this study shows they can be activated. Overexpressing a silent BGC in Streptomyces rimosus led to metabolite production, revealing complex regulation of these important gene clusters.

Keywords:
biosynthetic gene clustergene regulationgenome reductionoxytetracyclinerimocidin

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Area of Science:

  • Microbial genomics and secondary metabolite biosynthesis.
  • Investigating the regulation and activation of silent biosynthetic gene clusters (BGCs).

Background:

  • Numerous microbial genomes contain biosynthetic gene clusters (BGCs) with unknown structures, representing a potential source of novel natural products.
  • Many identified BGCs appear inactive ('silent'), hindering the discovery of new metabolites.
  • Understanding the regulation and biosynthesis of secondary metabolites from silent BGCs is crucial.

Purpose of the Study:

  • To analyze the expression of identified BGCs in Streptomyces rimosus ATCC 10970.
  • To investigate the reasons behind the inactivity of many BGCs.
  • To evaluate the potential of activating silent BGCs for metabolite production.

Main Methods:

  • Bioinformatic analysis of Streptomyces rimosus ATCC 10970 genome and BGCs.
  • Transcriptional analysis of identified BGCs.
  • Experimental evaluation of BGC deletion and overexpression effects on metabolite production.
  • Analysis of regulatory mechanisms for oxytetracycline and rimocidin biosynthesis.

Main Results:

  • Identified 48 BGCs in Streptomyces rimosus, with only ~15 structures predicted or identified.
  • Transcriptional analysis revealed high variability in BGC expression, with ~30% being silent.
  • Overexpression of a silent carotenoid (isorenieratene) BGC resulted in significant metabolite production.
  • Deletion of one silent BGC, derived from malonyl-coenzyme A, strongly affected oxytetracycline biosynthesis.

Conclusions:

  • Silent BGCs are likely functional and can be activated for metabolite production.
  • The expression of BGCs in Streptomyces rimosus is regulated by complex mechanisms.
  • Engineered Streptomyces rimosus strains serve as a valuable model for studying silent BGC expression.