Discovery of anti-Mycobacterium tuberculosis desertomycins from Streptomyces flavofungini TRM90047 based on genome mining and HSQC-TOCSY
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 leve...
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Published in | Scientific reports Vol. 14; no. 1; pp. 17006 - 8 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
24.07.2024
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-024-65702-0 |