Bioactivity-guided isolation identified the main antifungal compounds produced by as the new polyhydroxy-polyketides acrophialocinol () and acrophialocin (). Their biosynthesis was elucidated by heterologous reconstitution in 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 biosynthetic gene cluster.