Discovery of anti-Mycobacterium tuberculosis desertomycins from Streptomyces flavofungini TRM90047 based on genome mining and HSQC-TOCSY.
Sci Rep
; 14(1): 17006, 2024 07 24.
Article
en En
| MEDLINE
| ID: mdl-39043745
ABSTRACT
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 EC50 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Streptomyces
/
Simulación del Acoplamiento Molecular
/
Mycobacterium tuberculosis
/
Antituberculosos
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido