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 inScientific reports Vol. 14; no. 1; pp. 17006 - 8
Main Authors Wang, Lei, Reheman, Aikebaier, Wan, Chuanxing
Format Journal Article
LanguageEnglish
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
Online AccessGet full text

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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
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Issue 1
Keywords Desertomycin
HSQC-TOCSY
Anti
Genome mining
Anti-M. tb
Language English
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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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proquest
crossref
pubmed
springer
SourceType Open Website
Open Access Repository
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Index Database
Publisher
StartPage 17006
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
URI https://link.springer.com/article/10.1038/s41598-024-65702-0
https://www.ncbi.nlm.nih.gov/pubmed/39043745
https://www.proquest.com/docview/3083766361
https://www.proquest.com/docview/3084029939/abstract/
https://pubmed.ncbi.nlm.nih.gov/PMC11266358
https://doaj.org/article/03ed8698a7ca475e9dd487892aa0d8f1
Volume 14
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