Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products

authored by

Lukas Kahlert, Darlon Bernardi, Maurice Hauser, Laura P. Ióca, Roberto G. S. Berlinck, Elizabeth J. Skellam, Russell J. Cox

Abstract

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.

Organisation(s)

Institute of Organic Chemistry
Centre of Biomolecular Drug Research (BMWZ)

External Organisation(s)

Universidade de Sao Paulo
University of North Texas

Type

Article

Journal

Chemistry – A European Journal

Volume

27

Pages

11895-11903

No. of pages

9

Publication date

16.08.2021

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Catalysis, Organic Chemistry

Sustainable Development Goals

SDG 14 - Life Below Water

Electronic version(s)

https://doi.org/10.1002/chem.202101447 (Access: Open)