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Abstract <p>The genome of <i>Streptomyces lavendulae</i> subsp. <i>lavendulae</i> CCM 3239 contains 36 biosynthetic gene clusters (BGCs) that are cryptic or silent, except for the previously characterized aromatic polyketide auricin. In this work, we present a simple strategy to activate BGCs in this strain by replacing the native promoter with the strong <i>kasOp*</i> promoter via homologous recombination. This approach was validated by strong indigoidine production following insertion of <i>kasOp*</i> upstream of the silent <i>bpsA</i> gene. Using this strategy, we activated a silent BGC encoding a type I polyketide synthase (PKS). Interestingly, insertion of <i>kasOp*</i> at different positions within this BGC—upstream of the <i>SLAV_02840</i> and <i>SLAV_02776</i> genes—led to the production of distinct compounds, both exhibiting polyene spectral features and antifungal activity. Both compounds were isolated, and structural analysis revealed that they were similar to strevertenes; consequently, they were named strevertene A2 and X. A database search indicated that their structures corresponded to the known compounds RKGS-A2215A and AB023a. In silico analysis of the biosynthetic enzymes encoded by this strevertene (<i>stv</i>) BGC enabled us to propose a biosynthetic model consistent with the observed induction in the mutant strains <i>S. lavendulae kasOp::2776</i> and <i>S. lavendulae kasOp::2840</i>. The analysis also suggested that strevertene X is an intermediate in the formation of the final polyene, strevertene A2. Notably, strevertene X exhibited approximately twofold higher antifungal activity than strevertene A2.</p> Key points <p>• <i>Strategy for activating BGCs by introducing a strong kasOp* promoter.</i></p> <p>• <i>Efficient activation of the silent bpsA gene for indigoidine.</i></p> <p>• <i>Activation of silent BGC for type I PKS for polyenes strevertene A2 and X.</i></p>

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Activation of a gene cluster in Streptomyces lavendulae subsp. lavendulae CCM 3239 induced strevertene production

  • 期刊论文

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  • 发表日期：

    2026年6月15日

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  • Filip Opaterny,
  • Rachel Javorova,
  • Michal Soral,
  • Lubomira Feckova,
  • Dominika Csolleiova,
  • Renata Novakova,
  • Kamila Cholvadtova,
  • Iveta Uhliarikova,
  • Maria Kopacova,
  • Vladimir Patoprsty,
  • Bronislava Rezuchova,
  • Beatrica Sevcikova,
  • Jan Kormanec

摘要

Abstract

The genome of Streptomyces lavendulae subsp. lavendulae CCM 3239 contains 36 biosynthetic gene clusters (BGCs) that are cryptic or silent, except for the previously characterized aromatic polyketide auricin. In this work, we present a simple strategy to activate BGCs in this strain by replacing the native promoter with the strong kasOp* promoter via homologous recombination. This approach was validated by strong indigoidine production following insertion of kasOp* upstream of the silent bpsA gene. Using this strategy, we activated a silent BGC encoding a type I polyketide synthase (PKS). Interestingly, insertion of kasOp* at different positions within this BGC—upstream of the SLAV_02840 and SLAV_02776 genes—led to the production of distinct compounds, both exhibiting polyene spectral features and antifungal activity. Both compounds were isolated, and structural analysis revealed that they were similar to strevertenes; consequently, they were named strevertene A2 and X. A database search indicated that their structures corresponded to the known compounds RKGS-A2215A and AB023a. In silico analysis of the biosynthetic enzymes encoded by this strevertene (stv) BGC enabled us to propose a biosynthetic model consistent with the observed induction in the mutant strains S. lavendulae kasOp::2776 and S. lavendulae kasOp::2840. The analysis also suggested that strevertene X is an intermediate in the formation of the final polyene, strevertene A2. Notably, strevertene X exhibited approximately twofold higher antifungal activity than strevertene A2.

Key points

• Strategy for activating BGCs by introducing a strong kasOp* promoter.

• Efficient activation of the silent bpsA gene for indigoidine.

• Activation of silent BGC for type I PKS for polyenes strevertene A2 and X.