Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes

Background: The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents. Methods: This study integrates cultivation optimization, nuclear magnetic resonance (NMR) fingerprinting, and principal component analysis (PCA) to explore microbial...

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Main Authors: Jianying Han, Xueting Liu, Lixin Zhang, Ronald J. Quinn, Miaomiao Liu
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/1/108
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author Jianying Han
Xueting Liu
Lixin Zhang
Ronald J. Quinn
Miaomiao Liu
author_facet Jianying Han
Xueting Liu
Lixin Zhang
Ronald J. Quinn
Miaomiao Liu
author_sort Jianying Han
collection DOAJ
description Background: The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents. Methods: This study integrates cultivation optimization, nuclear magnetic resonance (NMR) fingerprinting, and principal component analysis (PCA) to explore microbial secondary metabolites as potential anti-TB agents. Results: Using the combined approach, 11 bioactive compounds were isolated and identified, all exhibiting anti-<i>Mycobacterium bovis</i> BCG activity. Notable findings include borrelidin, a potent threonyl-tRNA synthetase inhibitor with broad biological activities, and L-O-Lac-L-Val-D-O-Hiv-D-Val, a peptide isolated for the first time from a plant endophyte, demonstrating broad-spectrum antimicrobial activity. Additionally, elaiophylin and polycyclic tetramate macrolactams (PTMs) displayed significant bactericidal effects, with elaiophylin achieving complete BCG inhibition at 72 h and PTMs marking their first reported anti-TB activity. The study also identified bafilomycins as potent scaffolds for anti-TB drug development, showcasing rapid bactericidal activity at low MIC values. Conclusions: These findings emphasize the value of microbial metabolites as a reservoir of bioactive compounds and provide new avenues for developing next-generation anti-TB therapies.
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spelling doaj-art-6c2bc98b532247d18ac58c38349195ee2025-01-24T13:19:03ZengMDPI AGAntibiotics2079-63822025-01-0114110810.3390/antibiotics14010108Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from ActinomycetesJianying Han0Xueting Liu1Lixin Zhang2Ronald J. Quinn3Miaomiao Liu4Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaBackground: The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents. Methods: This study integrates cultivation optimization, nuclear magnetic resonance (NMR) fingerprinting, and principal component analysis (PCA) to explore microbial secondary metabolites as potential anti-TB agents. Results: Using the combined approach, 11 bioactive compounds were isolated and identified, all exhibiting anti-<i>Mycobacterium bovis</i> BCG activity. Notable findings include borrelidin, a potent threonyl-tRNA synthetase inhibitor with broad biological activities, and L-O-Lac-L-Val-D-O-Hiv-D-Val, a peptide isolated for the first time from a plant endophyte, demonstrating broad-spectrum antimicrobial activity. Additionally, elaiophylin and polycyclic tetramate macrolactams (PTMs) displayed significant bactericidal effects, with elaiophylin achieving complete BCG inhibition at 72 h and PTMs marking their first reported anti-TB activity. The study also identified bafilomycins as potent scaffolds for anti-TB drug development, showcasing rapid bactericidal activity at low MIC values. Conclusions: These findings emphasize the value of microbial metabolites as a reservoir of bioactive compounds and provide new avenues for developing next-generation anti-TB therapies.https://www.mdpi.com/2079-6382/14/1/108tuberculosisactinomycetesborrelidinelaiophylinpolycyclic tetramate macrolactamsbafilomycin
spellingShingle Jianying Han
Xueting Liu
Lixin Zhang
Ronald J. Quinn
Miaomiao Liu
Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
Antibiotics
tuberculosis
actinomycetes
borrelidin
elaiophylin
polycyclic tetramate macrolactams
bafilomycin
title Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
title_full Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
title_fullStr Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
title_full_unstemmed Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
title_short Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
title_sort nuclear magnetic resonance fingerprinting and principal component analysis strategies lead to anti tuberculosis natural product discovery from actinomycetes
topic tuberculosis
actinomycetes
borrelidin
elaiophylin
polycyclic tetramate macrolactams
bafilomycin
url https://www.mdpi.com/2079-6382/14/1/108
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