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Onydecalins, Fungal Polyketides with Anti-Histoplasma and Anti-TRP Activity
- Lin, Zhenjian, Phadke, Sujal, Lu, Zhenyu, Beyhan, Sinem, Abdel Aziz, May H., Reilly, Chris, Schmidt, Eric W.
- Journal of natural products 2018 v.81 no.12 pp. 2605-2611
- Histoplasma capsulatum, animal pathogenic fungi, biosynthesis, fermentation, fungal growth, polyketides, pyridones, transient receptor potential channels
- We report an unusual 3-substituted pyridine polyketide, onydecalin A (1), which was obtained along with 2 as a major constituent from the fungus Aioliomyces pyridodomos (order: Onygenales) following a two-month fermentation. Feeding studies demonstrated that the pyridine subunit originates via an unprecedented biosynthetic process in comparison to other polyketide-linked pyridines or derivatives such as pyridones. The slow growth of the fungus led us to perform a one-year fermentation, leading to production of compounds 2–4 as the major constituents. These compounds showed modest but selective inhibition against a variety of transient receptor potential channels, as well as against the human pathogenic fungus Histoplasma capsulatum.