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Metabolic Competition between Non-reducing Polyketide Synthases Drives Hidden Chemodiversity in Deep-Sea Fungus
Jun Wu1, Wei-Chen Chen1,2, Bowei Wen3,4
1Department of Radiation and Medical Oncology, Zhongnan Hospital, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
None:
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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