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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
International journal of molecular sciences
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/42196141/ |
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Table of Contents:
- Genome Mining of Deep-Sea Cold Seep-Derived Fungus Reveals a Laccase-Fasciclin System Modulating Regioselective Naphthopyranone Dimerization. Li, Hongcheng Li, Zhiting Sun, Junpeng Yang, Xiaoyu Xing, Kaishuai Shi, Meixin Xiao, Fei Li, Wenli Laccase Multigene Family Penicillium Polyketide Synthases Dimerization Naphthalenes Genome, Fungal Naphthopyranones represent a structurally diverse family of fungal polyketides exhibiting a broad range of biological activities, including antibacterial, antifungal, and cytotoxic properties. Despite extensive investigations of terrestrial-derived naphthopyranones, the biosynthetic machinery responsible for their production in marine fungi has remained unexplored. Here, we report the first characterization of naphthopyranone biosynthetic gene clusters (BGCs) from a deep-sea-derived fungus. Genome mining of the cold seep-associated OUCF108 revealed two highly homologous polyketide synthase gene clusters, and . Comparative transcriptomics combined with targeted disruption of the core PKS gene demonstrated that is the essential BGC responsible for ()-semivioxanthin () production. Stepwise reconstruction of the pathway in NSAR1 unraveled the complete biosynthetic route from the heptaketide precursor -toralactone () to ()-semivioxanthin () and its dimeric derivatives. In vitro biochemical characterization revealed that the -methyltransferase PigN2 catalyzes regioselective 6--methylation with relaxed substrate specificity, that the laccase PigF2 mediates oxidative dimerization of to afford dimeric derivatives, and that the fasciclin-like protein PigG2 alters this default regiochemistry, affording abundant alternative regioisomeric dimers alongside the 5,5'-linked product. Notably, a new naphthopyranone derivative, -4-hydroxy-toralactone (), was isolated and structurally elucidated. Antimicrobial evaluation of all isolated compounds revealed that exhibits moderate antifungal activity against the multidrug-resistant pathogen (MIC = 12.5 μg mL). Structure-activity relationship analysis identified the C-4 hydroxyl moiety is critical for activity. This study highlights the potential of deep-sea fungi as an untapped reservoir of bioactive naphthopyranones and provides enzymatic insights for the construction of regioselectively coupled biaryl scaffolds.