Antibacterial epipolythiodioxopiperazine and unprecedented sesquiterpene from Pseudallescheria boydii, a beetle (coleoptera)-associated fungus

Abstract

Pseudallescheria boydii residing in the gut of coleopteran (Holotrichia parallela) larva produces four new epipolythiodioxopiperazine (ETP) boydines A–D (3–6) and two novel sesquiterpene boydenes A (7) and B (10), in addition to bisdethiobis(methylthio)-deacetylaranotin (1), bisdethiodi(methylthio)-deacetylapoaranotin (2), AM6898 A (8) and ovalicin (9). The structure elucidation was accomplished by a combination of spectral methods with quantum chemical calculations of optical rotations and electronic circular dichroism (ECD) spectra. Boydine B (4) was shown to be active against the clinical strains Bifidobacterium sp., Veillonella parvula, Anaerostreptococcus sp., Bacteroides vulgatus and Peptostreptococcus sp. with an MIC range of 0.2–0.8 μM, and the pharmacophore 3-hydroxy-2,4,6-trimethyl-5-oxooct-6-enoyl chain of 4 was shown to have (2R,3S,4S)-configurations. Boydene A (7) possessed an unprecedented carbon skeleton, suggesting an unusual biochemistry that allows an intramolecular Aldol addition in the fungus. Collectively, the finding may inspire the discovery of new antibacterial agents and the understanding on biosyntheses of polythiodioxopiperazine and sesquiterpene metabolites.