Dong Liao-Bin, Rudolf Jeffrey D, Deng Ming-Rong, Yan Xiaohui, Shen Ben
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Department of Molecular Medicine, Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Chembiochem. 2018 May 27. doi: 10.1002/cbic.201800285.
Although genome mining has advanced the identification, discovery, and study of microbial natural products, the discovery of bacterial diterpenoids continues to lag behind. Herein, we report the identification of 66 putative producers of novel bacterial diterpenoids, and the discovery of the tiancilactone (TNL) family of antibiotics, by genome mining of type II diterpene synthases that do not possess the canonical DXDD motif. The TNLs, which are broad-spectrum antibiotics with moderate activities, are produced by both Streptomyces sp. CB03234 and Streptomyces sp. CB03238 and feature a highly functionalized diterpenoid skeleton that is further decorated with chloroanthranilate and γ-butyrolactone moieties. Genetic manipulation of the tnl gene cluster resulted in TNL congeners, which provided insights into their biosynthesis and structure-activity relationships. This work highlights the biosynthetic potential that bacteria possess to produce diterpenoids and should inspire continued efforts to discover terpenoid natural products from bacteria.
尽管基因组挖掘推动了微生物天然产物的鉴定、发现及研究，但细菌二萜类化合物的发现仍相对滞后。在此，我们通过对不具有典型DXDD基序的II型二萜合酶进行基因组挖掘，报告了66种新型细菌二萜类化合物推定产生菌的鉴定，以及抗生素天丝内酯（TNL）家族的发现。TNL是一类具有中等活性的广谱抗生素，由链霉菌属CB03234菌株和链霉菌属CB03238菌株产生，其特征是具有高度官能化的二萜骨架，并进一步被氯邻氨基苯甲酸酯和γ-丁内酯部分修饰。对tnl基因簇进行遗传操作产生了TNL同系物，这为其生物合成及构效关系提供了见解。这项工作突出了细菌产生二萜类化合物的生物合成潜力，并应激励人们继续努力从细菌中发现萜类天然产物。
