Biosynthesis of the Antifungal Polyhydroxy-Polyketide Acrophialocinol
Carsten Wieder, Moritz Künzer, Rainer Wiechert, Kevin Seipp, Karsten Andresen, P. A. Stark, Anja Schüffler, Till Opatz, Eckhard Thines
Abstract
High Resolution Image Download MS PowerPoint Slide 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.