Title | Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Zhu C, Xu B, Adpressa DA, Rudolf JD, Loesgen S |
Journal | Angew Chem Int Ed Engl |
Volume | 60 |
Issue | 25 |
Pagination | 14163-14170 |
Date Published | 2021 Jun 14 |
ISSN | 1521-3773 |
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. |
DOI | 10.1002/anie.202102453 |
Alternate Journal | Angew Chem Int Ed Engl |
PubMed ID | 33780586 |
Grant List | GM124461 / NH / NIH HHS / United States CH1808717 / / National Science Foundation / GM124461 / NH / NIH HHS / United States |