ArticleNature microbiology2022
Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Identification of a Pair of Linear or Cyclic Naturally Inspired Bifunctional Lipopeptide Antibiotics That Overcome Antimicrobial Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hijacking the Electron Train: Menaquinone-Binding Antimicrobial Peptides.Chembiochem : a European journal of chemical biology · 2025Review
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- WalK(S221P) Mutation Promotes the Production ofMicroorganisms · 2025Article
- Synthetic-bioinformatic natural product-inspired peptides.Natural product reports · 2025Review
- Discovery of a family of menaquinone-targeting cyclic lipodepsipeptides for multidrug-resistant Gram-positive pathogens.Communications biology · 2024Article
- Cinnamosyn, a Cinnamoylated Synthetic-Bioinformatic Natural Product with Cytotoxic Activity.Organic letters · 2024Article
- A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates.ACS infectious diseases · 2023Article
- Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial peritonitis.Biomaterials · 2023Article
- Present and future outlooks on environmental DNA-based methods for antibiotic discovery.Current opinion in microbiology · 2023Review
- Interplay of emerging and established technologies drives innovation in natural product antibiotic discovery.Current opinion in microbiology · 2023Review
- Returning to Nature for the Next Generation of Antimicrobial Therapeutics.Antibiotics (Basel, Switzerland) · 2023Review
- Article
- Modern Trends in Natural Antibiotic Discovery.Life (Basel, Switzerland) · 2023Review
- Next-generation synthetic biology approaches for the accelerated discovery of microbial natural products.Engineering microbiology · 2023Review
- Article
- The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies.Antibiotics (Basel, Switzerland) · 2022Review
- Bottom-up synthetic biology approach for improving the efficiency of menaquinone-7 synthesis in Bacillus subtilis.Microbial cell factories · 2022Article
- Polyene Macrolactams from Marine and Terrestrial Sources: Structure, Production Strategies, Biosynthesis and Bioactivities.Marine drugs · 2022Review
- Uncovering interactions between mycobacterial respiratory complexes to target drug-resistantFrontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The emergence of multidrug-resistant bacteria poses a threat to global health and necessitates the development of additional in vivo active antibiotics with diverse modes of action. Directly targeting menaquinone (MK), which plays an important role in bacterial electron transport, is an appealing, yet underexplored, mode of action due to a dearth of MK-binding molecules. Here we combine sequence-based metagenomic mining with a motif search of bioinformatically predicted natural product structures to identify six biosynthetic gene clusters that we predicted encode MK-binding antibiotics (MBAs). Their predicted products (MBA1-6) were rapidly accessed using a synthetic bioinformatic natural product approach, which relies on bioinformatic structure prediction followed by chemical synthesis. Among these six structurally diverse MBAs, four make up two new MBA structural families. The most potent member of each new family (MBA3, MBA6) proved effective at treating methicillin-resistant Staphylococcus aureus infection in a murine peritonitis-sepsis model. The only conserved feature present in all MBAs is the sequence 'GXLXXXW', which we propose represents a minimum MK-binding motif. Notably, we found that a subset of MBAs were active against Mycobacterium tuberculosis both in vitro and in macrophages. Our findings suggest that naturally occurring MBAs are a structurally diverse and untapped class of mechanistically interesting, in vivo active antibiotics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.