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Updated: May 31, 2025

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Biosynthesis of the Antifungal Polyhydroxy-Polyketide Acrophialocinol
Carsten Wieder1,2, Moritz Künzer1, Rainer Wiechert3
1Institute of Molecular Physiology, Johannes Gutenberg-University, Hanns-Dieter-Huesch-Weg 17, D-55128 Mainz, Germany.
None:
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.
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