State Key Laboratory Breeding Base for The Protection and Utilization of Biological Resources in TarimBasin Co-Funded By Xinjiang Production & Construction Corps and The Ministry of Science & Technology / College of Life Science and Technology, Tarim University, Alar, 843300, China.
College of Animal Science and Technology, Tarim University, Alar, 843300, China.
Sci Rep. 2024 Jul 24;14(1):17006. doi: 10.1038/s41598-024-65702-0.
Tuberculosis caused by Mycobacterium tuberculosis (M. tb) is a major public health problem with high morbidity and mortality worldwide. In our previous study, we found that a fermentation product of Streptomyces flavofungini TRM90047 exhibited anti-M. tb activity and decreased the expression level of several genes, including rpsL, Rplc and ClpC1. Guided by heteronuclear single quantum correlation-total correlation spectroscopy (HSQC-TOCSY) fingerprints and genome mining, we isolated two new 44-membered macrolides, desertomycin 44-1 (1) and desertomycin 44-2 (2), together with known desertomycin A (3) from S. flavofungini TRM90047. Three desertomycins showed anti-M. tb activity. The EC values of desertomycin A, desertomycin 44-1 and desertomycin 44-2 were 25 µg/mL, 25 µg/mL and 50 µg/mL, respectively. Molecular docking analyses revealed that the isolated desertomycins bound well to the RPSL, RPLC and CLPC1 proteins. In the present study, we describe the discovery of new anti-M. tb compounds guided by genome mining, HSQC-TOCSY and anti-M. tb bioassays.
结核分枝杆菌（M. tb）引起的结核病是一个全球性的重大公共卫生问题，发病率和死亡率都很高。在我们之前的研究中，我们发现链霉菌 TRM90047 的发酵产物具有抗结核分枝杆菌的活性，并降低了几个基因的表达水平，包括 rpsL、Rplc 和 ClpC1。根据异核单量子相关-全相关光谱（HSQC-TOCSY）指纹图谱和基因组挖掘，我们从 S. flavofungini TRM90047 中分离出两种新的 44 元大环内酯类化合物，分别为荒漠霉素 44-1（1）和荒漠霉素 44-2（2），以及已知的荒漠霉素 A（3）。三种荒漠霉素均具有抗结核分枝杆菌活性。荒漠霉素 A、荒漠霉素 44-1 和荒漠霉素 44-2 的 EC 值分别为 25μg/mL、25μg/mL 和 50μg/mL。分子对接分析表明，分离出的荒漠霉素与 RPSL、RPLC 和 CLPC1 蛋白结合良好。在本研究中，我们描述了在基因组挖掘、HSQC-TOCSY 和抗结核分枝杆菌生物测定的指导下，发现了新的抗结核分枝杆菌化合物。
