Discovery of sesquiterpenoids from an actinomycete Crossiella cryophila through genome mining and heterologous expression.

Bioorg Chem

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Published: May 2024

Genome mining of the Actinomycete Crossiella cryophila facilitated the discovery of a minimal terpenoid biosynthetic gene cluster of cry consisting of a class I terpene cyclase CryA and a CYP450 monooxygenase CryB. Heterologous expression of cry allowed the isolation and characterization of two new sesquiterpenoids, ent-viridiflorol (1) and cryophilain (2). Notably, cryophilain (2) possesses a 5/7/3-fused tricyclic skeleton bearing a distinctive bridgehead hydroxy group. The combined in vivo and in vitro experiments revealed that CryA, the first ent-viridiflorol terpene cyclase, catalyzes farnesyl diphosphate to form the 5/7/3 sesquiterpene core scaffold and P450 CryB serves as a tailoring enzyme responsible for installing a hydroxy group at the bridgehead carbon.

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http://dx.doi.org/10.1016/j.bioorg.2024.107308DOI Listing

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