Pinpointing Pseurotins from a Marine-Derived Aspergillus as Tools for Chemical Genetics Using a Synthetic Lethality Yeast Screen

A new compound of mixed polyketide synthase–nonribosomal peptide synthetase (PKS/NRPS) origin, 11-O-methylpseurotin A (1), was identified from a marine-derived Aspergillus fumigatus. Bioassay-guided fractionation using a yeast halo assay with wild-type and cell cycle-related mutant strains of Saccharomyces cerevisiae resulted in the isolation of 1, which selectively inhibited a Hof1 deletion strain. Techniques including 1D and 2D NMR, HRESIMS, optical rotation, J-based analysis, and biosynthetic parallels were used in the elucidation of the planar structure and absolute configuration of 1. A related known compound, pseurotin A (2), was also isolated and found to be inactive in the yeast screen.