Combinatorial Biosynthesis of Terpenoids through Mixing-and-Matching Sesquiterpene Cyclase and Cytochrome P450 Pairs.

Org Lett

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Published: July 2022

Terpenoids are an important class of natural products with diverse structures and bioactivities. Their hydrocarbon scaffolds are mainly derived from the terpenes produced by terpene cyclases (TCs). Otherwise, new hydrocarbon scaffolds can be achieved through oxidative rearrangement catalyzed by oxygenases such as P450s. Herein, we report the functional characterization of α/β--bergamotene-producing TCs and their multifunctional P450 partners mined from different fungal species. In addition, novel sesquiterpenoids with hydrocarbon scaffolds different from bergamotenes were generated by combinatorial biosynthesis through mixing-and-matching these TC and P450 pairs. Our results provide a successful example of expanding the chemical diversity of terpenoids by combining genome mining and synthetic biology.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899527PMC
http://dx.doi.org/10.1021/acs.orglett.2c01785DOI Listing

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