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Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products
Author(s) -
Kahlert Lukas,
Bernardi Darlon,
Hauser Maurice,
Ióca Laura P.,
Berlinck Roberto G. S.,
Skellam Elizabeth J.,
Cox Russell J.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101447
Subject(s) - oxidative phosphorylation , oxidative decarboxylation , decarboxylation , chemistry , monooxygenase , biochemistry , heterologous expression , biosynthesis , stereochemistry , enzyme , gene , cytochrome p450 , recombinant dna , catalysis
The mycotoxin terrein is derived from the C 10 ‐precursor 6‐hydroxymellein (6‐HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin‐dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6‐HM. The reactive intermediate is further hydroxylated by the second FMO TerD to yield a highly oxygenated aromatic species, but further reconstitution of the pathway was hampered. A related BGC was identified in the marine‐derived Roussoella sp . DLM33 and confirmed by heterologous expression. These studies demonstrate that the biosynthetic pathways of terrein and related (polychlorinated) congeners diverge after oxidative decarboxylation of the lactone precursor that is catalyzed by a conserved FMO and further indicate that early dehydration of the side chain is an essential step.