TitleDiscovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhu C, Xu B, Adpressa DA, Rudolf JD, Loesgen S
JournalAngew Chem Int Ed Engl
Volume60
Issue25
Pagination14163-14170
Date Published2021 Jun 14
ISSN1521-3773
Abstract

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 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.

DOI10.1002/anie.202102453
Alternate JournalAngew Chem Int Ed Engl
PubMed ID33780586
Grant ListGM124461 / NH / NIH HHS / United States
CH1808717 / / National Science Foundation /
GM124461 / NH / NIH HHS / United States