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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24.07.2024
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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 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. |
---|---|
AbstractList | 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. 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. 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. 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.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. 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. |
ArticleNumber | 17006 |
Author | Wan, Chuanxing Wang, Lei Reheman, Aikebaier |
Author_xml | – sequence: 1 givenname: Lei surname: Wang fullname: Wang, Lei organization: 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 – sequence: 2 givenname: Aikebaier surname: Reheman fullname: Reheman, Aikebaier organization: College of Animal Science and Technology, Tarim University – sequence: 3 givenname: Chuanxing surname: Wan fullname: Wan, Chuanxing email: wanchuanxing@163.com organization: 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 |
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Keywords | Desertomycin HSQC-TOCSY Anti Genome mining Anti-M. tb |
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Snippet | Tuberculosis caused by
Mycobacterium tuberculosis
(
M. tb
) is a major public health problem with high morbidity and mortality worldwide. In our previous... Tuberculosis caused by Mycobacterium tuberculosis (M. tb) is a major public health problem with high morbidity and mortality worldwide. In our previous study,... Abstract Tuberculosis caused by Mycobacterium tuberculosis (M. tb) is a major public health problem with high morbidity and mortality worldwide. In our... |
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SubjectTerms | 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 |
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Title | Discovery of anti-Mycobacterium tuberculosis desertomycins from Streptomyces flavofungini TRM90047 based on genome mining and HSQC-TOCSY |
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