美国佛罗里达大学惠特尼海洋生物科学实验室Sandra Loesgen团队，发现并生物合成了结构动态抗菌二萜化合物。 相关研究成果发表在2021年3月29日出版的《德国应用化学》。

研究人员从土壤链霉菌（CL12-4）中分离到一种新的双环二萜，苯二萜酸。对细菌基因组进行了测序，鉴定了负责生物合成的基因簇，验证了萜烯合成酶的功能，并异源合成了核心二萜。生物信息学分析表明，该菌株在系统发育上是独特的，具有9种萜烯合成酶。通过广泛的光谱分析，包括Mosher分析、基于J的耦合分析和基于稀疏NMR衍生实验约束的计算，发现新的反式熔合双环[8.4.0]十四烷具有绝对构型。

有趣的是，苯二萜酸在溶液中以两种不同的环翻转双环构象存在，旋转势垒约为16 kcal mol-1。二萜对革兰氏阳性菌（包括甲氧西林和耐多药金黄色葡萄球菌）具有中度抗菌活性。这是首次从细菌中分离到eunicellane型二萜，并首次鉴定了负责构建尤尼西兰eunicellane支架的二萜合酶和生物合成基因簇。

附：英文原文

Title: Discovery and biosynthesis of a structurally dynamic antibacterial diterpenoid

Author: Chenxi Zhu, Baofu Xu, Donovon A. Adpressa, Jeffrey D. Rudolf, Sandra Loesgen

Issue&Volume: 2021-03-29

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‐1 in solution. The diterpenes exhibit moderate antibacterial activity against Gram‐positive bacteria including methicillin and multi‐drug resistant Staphylococcus aureus. This is the first isolation 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

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202102453