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Biosynthetic Machinery of 6‐Hydroxymellein Derivatives Leading to Cyclohelminthols and Palmaenones
Author(s) -
Ugai Takahiro,
Minami Atsushi,
Tanaka Shizuya,
Ozaki Taro,
Liu Chengwei,
Shigemori Hideyuki,
Hashimoto Masaru,
Oikawa Hideaki
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900404
Subject(s) - biogenesis , polyketide , biosynthesis , heterologous expression , aspergillus oryzae , biochemistry , biology , gene , chemistry , enzyme , recombinant dna , stereochemistry
Oxygenated cyclopentene systems are unique structural motifs found in fungal polyketides such as terrein, cyclohelminthols, and palmaenones. Here we report the identification of the biosynthetic gene clusters for cyclohelminthols and palmaenones and the functional characterization of the polyketide synthases and halogenases involved in the construction of 6‐hydroxymellein derivatives. Heterologous expression in Aspergillus oryzae demonstrated that 6‐hydroxymellein is a common biosynthetic intermediate and that chlorination occurs in the early stages of its products’ biosynthesis. This was further confirmed by in vitro enzymatic reactions conducted in the presence of recombinant proteins. Plausible means of biogenesis of fungal polyketides from 6‐hydroxymellein derivatives, additionally supported by the reported labeling patterns of terrein and structurally related fungal polyketides, are also discussed. This study sets the stage for elucidation of the biosynthetic machinery of fungal polyketides of this type.