10.1002/anie.201404804
The study primarily focuses on elucidating the biosynthetic pathway of pseurotins, a family of structurally related Aspergillal natural products with significant bioactivity. Researchers systematically deleted pseurotin biosynthetic genes in Aspergillus fumigatus and characterized tailoring enzymes in vivo and in vitro to determine biosynthetic intermediates and the genes responsible for their formation. Key chemicals used in the study include azaspirene, the predominant precursor, and pseurotin A, a compound of interest. The study also identified PsoF, a bifunctional fusion protein consisting of a C-methyltransferase and an FAD-containing monooxygenase domain, which plays a crucial role in the methylation of the polyketide backbone and the formation of the epoxide group in pseurotins. Other chemicals mentioned include N-acetylcysteamine (NAC) thioester, used as a mimic for the natural substrate in the C-methylation step, and various pseurotin-type compounds and their intermediates, which were analyzed for their roles in the biosynthetic pathway. The purpose of using these chemicals was to understand the combinatorial nature of pseurotin biosynthesis, the formation of the spiro-ring core structure, and the generation of chemical diversity within the pseurotin family of compounds.
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