Insights into the Metabolomic Capacity of Podaxis and Isolation of Podaxisterols A–D, Ergosterol Derivatives Carrying Nitrosyl Cyanide-Derived Modifications

• Published in: Journal of natural products (Washington, D.C.) Vol. 85; no. 9; pp. 2159 - 2167
• Main Authors: Guo, Huijuan, Daniel, Jan-Martin, Seibel, Elena, Burkhardt, Immo, Conlon, Benjamin H., Görls, Helmar, Vassão, Daniel Giddings, Dickschat, Jeroen S., Poulsen, Michael, Beemelmanns, Christine
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 23.09.2022; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; AFRICA
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.2c00380

Cultures of a termite-associated and a free-living member of the fungal genus Podaxis, revived from spores maintained in century-old herbarium collections, were analyzed for their insecticidal and antimicrobial effects. Their secondary metabolomes were explored to uncover possible adaptive mechanisms of termite association, and dereplication of LC-HRMS/MS data sets led to the isolation of podaxisterols A–D (1–4), modified ergosterol derivatives that result from a Diels–Alder reaction with endogenous nitrosyl cyanide. Chemical structures were determined based on HRMS/MS and NMR analyses as well as X-ray crystallography. The putative origin of the endogenous fungal nitrosyl cyanide and ergosterol derivatives is discussed based on results obtained from stable isotope experiments and in silico analysis. Our “omics”-driven analysis of this underexplored yet worldwide distributed fungal genus builds a foundation for studies on a potential metabolic adaptations to diverse lifestyles.