Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine Bridge Enzyme-like Intramolecular Aldolase.

Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine Bridge Enzyme-like Intramolecular Aldolase.

Chemistry. 2019 Sep 25;:

Authors: Li H, Hu J, Wei H, Solomon PS, Stubbs KA, Chooi YH

Abstract
The aldol reaction is one of the most fundamental stereocontrolled carbon-carbon bond-forming reactions and is mainly catalyzed by aldolases in Nature. Despite aldol reaction has been widely proposed to be involved in fungal secondary metabolite biosynthesis, dedicated aldolase that catalyze stereoselective aldol reaction has rarely been reported in fungi. Here, we activated a cryptic polyketide biosynthetic gene cluster that was upregulated in the fungal wheat pathogen Parastagonospora nodorum during plant infection and it resulted in the production of the phytotoxic stemphyloxin II ( 1 ). Via heterologous reconstruction of the biosynthetic pathway and in vitro assay using cell-free lysate from Aspergillus nidulans we demonstrated a berberine bridge enzyme (BBE)-like protein SthB catalyzes an intramolecular aldol reaction to establish the bridged tricyclo[6.2.2.0 2,7 ]dodecane skeleton in the post-assembly tailoring step. The characterization of SthB as an aldolase enriches the catalytic toolbox of classic reactions and the functional diversities of the BBE superfamily enzymes.

PMID: 31553484 [PubMed – as supplied by publisher]

Source: Industry