Biosynthetic machinery of 6-hydroxymellein derivatives leading to cyclohelminthols and palmaenones.
Chembiochem. 2019 Jul 12;:
Authors: Ugai T, Minami A, Tanaka S, Ozaki T, Liu C, Shigemori H, Hashimoto M, Oikawa H
Oxygenated cyclopentene is a unique structural motif found in fungal polyketides such as terrein, cyclohelminthols, and palmaenones. Here, we report the identification of the biosynthetic gene clusters of cyclohelminthols and palmaenones and the functional characterization of the polyketide synthases and halogenases participating in the construction of 6-hydroxymellein derivatives. The heterologous expression in Aspergillus oryzae demonstrated that 6-hydroxymellin is a common biosynthetic intermediate and that chlorination occurs in the early stage of their biosynthesis. The latter was further confirmed by in vitro enzymatic reactions using recombinant proteins. Together with the reported labeling patterns of terrein and the structurally related fungal polyketide, the plausible biogenesis from 6-hydroxymellin derivatives to fungal polyketides is also discussed. The present study sets the stage to elucidate the biosynthetic machinery of this type of fungal polyketide.
PMID: 31298454 [PubMed – as supplied by publisher]