Discovery of anti-Mycobacterium tuberculosis desertomycins from Streptomyces flavofungini TRM90047 based on genome mining and HSQC-TOCSY

• Published in: Scientific reports Vol. 14; no. 1; pp. 17006 - 8
• Main Authors: Wang, Lei, Reheman, Aikebaier, Wan, Chuanxing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/45; Anti-M. tb; Antitubercular Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bioassays; Bioinformatics; Desertomycin; Fermentation; Genome mining; Genome, Bacterial; Genomes; Genomics; HSQC-TOCSY; Humanities and Social Sciences; Macrolides - chemistry; Macrolides - pharmacology; Microbial Sensitivity Tests; Molecular Docking Simulation; Morbidity; multidisciplinary; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Public health; Science; Science (multidisciplinary); Spectroscopy; Streptomyces; Streptomyces - genetics; Streptomyces - metabolism; Tuberculosis; Desertomycin; HSQC-TOCSY; Anti; Genome mining; Anti-M. tb
• ISSN: 2045-2322; 2045-2322
• 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 50 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.