Biosynthesis of the Antifungal Polyhydroxy-Polyketide Acrophialocinol.

Bioactivity-guided isolation identified the main antifungal compounds produced by Acrophialophora levis as the new polyhydroxy-polyketides acrophialocinol (1) and acrophialocin (2). Their biosynthesis was elucidated by heterologous reconstitution in Aspergillus oryzae and involves an α-ketoglutarate-dependent dioxygenase-catalyzed α-hydroxylation, resulting in the formation of a tertiary alcohol that is indispensable for antifungal activity. Furthermore, self-resistance toward the polyhydroxy-polyketides is mediated by a conserved RTA1-like protein encoded in the acr biosynthetic gene cluster.