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February 2, 2026Organic Letters0 citations

Metabolic Competition between Non-reducing Polyketide Synthases Drives Hidden Chemodiversity in Deep-Sea Fungus Talaromyces radicus

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JWJun WuWCWenxing ChenBWBowei Wen

Key Points

  • This research investigates how metabolic competition between certain enzymes affects compound diversity in Talaromyces radicus.
  • Genome mining of Talaromyces radicus to identify non-reducing polyketide synthases (nrPKSs)
  • Multiomics analysis to study precursor competition
  • Gene deletion to assess effects on compound production
  • Heterologous expression to evaluate enzyme activity
  • Deletion of Tr4942 led to the activation of nine new chromone derivatives and four new naphthoquinone derivatives
  • Compound 8 exhibited strong anti-inflammatory effects
  • Identified compounds demonstrated significant pro-angiogenic and anti-inflammatory activities

Abstract

Genome mining of Talaromyces radicus WHUF04045 identified two unusual nrPKSs (Tr4942 and Tr2381) with distinct release mechanisms, whose precursor competition was revealed by multiomics, gene deletion, and heterologous expression. Deletion of Tr4942 activated nine new chromone derivatives (1-9) and four new naphthoquinone derivatives (11-14), which displayed significant pro-angiogenic and anti-inflammatory activities, with compound 8 showing significant anti-inflammatory effects via modulation of the NF-κB signaling pathway.

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Cite This Study

Wu et al. (2026) studied this question.

synapsesocial.com/papers/6980fcb6c1c9540dea80e794https://doi.org/10.1021/acs.orglett.5c05307
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