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

Wu J, Chen W C, Wen B, Chen J, Yang Z, Lu K, Yao Z, Guo Z, Qiu H, Deng Z, Li N, Cai Y S, Hong K.

Org. Lett. 2026

https://doi.org/10.1021/acs.orglett.5c05307

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.