Non‐Canonical C16 Homoterpene Biosynthesis Widespread in Actinobacteria
Year: 2024
Type: article
Abstract: A novel biosynthetic pathway towards the rare and underexplored non‐canonical family of homoterpenes was discovered in actinobacteria through targeted genome mining and enzymatic in vitro reconstitution. The pathway comprises initial methylation‐induced double bond isomerization of farnesyl diphosphate (FPP) to (2E,7E)‐6‐methyl‐farnesyl diphosphate, catalyzed by a novel family of methyltransferases with unique dual function. The resulting linear C16 double bond isomer of FPP constitutes the specific substrate for a distinct family of type I terpene cyclases, catalyzing diverse cyclization reactions. Functional characterization of nine enzyme pairs led to discovery of five unprecedented homoterpene natural products. The enzymological novelty enables the development of novel biocatalytic and genetically programmable synthetic strategies towards methylated terpenoids with potentially unique properties (“magic methyl effect”).
Authors: Tatjana Reuter, Lars Dieminger, Sarah Steidle, Katrin Zoller, Maximilian Holocher, Lin Zhou, Dominik Matthias Hanauska, Katharina Racz, Lena Barra
Institution: University of Konstanz
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
OpenAlex ID: W4404610201