Characterisation of the biosynthetic pathway to agnestins A and B reveals the reductive route to chrysophanol in fungi

Two new dihydroxy-xanthone metabolites, agnestins A and B, were isolated from <i>Paecilomyces variotii</i> along with a number of related benzophenones and xanthones including monodictyphenone. The structures were elucidated by NMR analyses and X-ray crystallography. The agnestin (<i>agn</i>) biosynthetic gene cluster was identified and targeted gene disruptions of the PKS, Baeyer-Villiger monooxygenase, and other oxido-reductase genes revealed new details of fungal xanthone biosynthesis. In particular, identification of a reductase responsible for <i>in vivo</i> anthraquinone to anthrol conversion confirms a previously postulated essential step in aromatic deoxygenation of anthraquinones, <i>e.g.</i> emodin to chrysophanol.