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Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid
Author(s) -
Zhu Chenxi,
Xu Baofu,
Adpressa Donovon A.,
Rudolf Jeffrey D.,
Loesgen Sandra
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202102453
Subject(s) - diterpene , terpenoid , stereochemistry , gene cluster , bicyclic molecule , biosynthesis , streptomyces , terpene , strain (injury) , bacteria , antibacterial activity , atp synthase , biology , chemistry , biochemistry , gene , genetics , anatomy
A new bicyclic diterpenoid, benditerpenoic acid, was isolated from soil‐dwelling Streptomyces sp. (CL12‐4). We sequenced the bacterial genome, identified the responsible biosynthetic gene cluster, verified the function of the terpene synthase, and heterologously produced the core diterpene. Comparative bioinformatics indicated this Streptomyces strain is phylogenetically unique and possesses nine terpene synthases. The absolute configurations of the new trans ‐fused bicyclo[8.4.0]tetradecanes were achieved by extensive spectroscopic analyses, including Mosher's analysis, J ‐based coupling analysis, and computations based on sparse NMR‐derived experimental restraints. Interestingly, benditerpenoic acid exists in two distinct ring‐flipped bicyclic conformations with a rotational barrier of ≈16 kcal mol −1 in solution. The diterpenes exhibit moderate antibacterial activity against Gram‐positive bacteria including methicillin and multi‐drug resistant Staphylococcus aureus . This is a rare example of an eunicellane‐type diterpenoid from bacteria and the first identification of a diterpene synthase and biosynthetic gene cluster responsible for the construction of the eunicellane scaffold.