ArticleAntimicrobial agents and chemotherapy2007
Structure and biosynthesis of heat-stable antifungal factor (HSAF), a broad-spectrum antimycotic with a novel mode of action.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 268 citations in OpenAlex.
- A bacterial-killing type IV secretion system as a hidden antifungal device.Science advances · 2026Article
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- Chemoselective Difluorination of Tetramic Acids in Water.ACS omega · 2026Article
- Hfq modulates system-wide regulatory networks controlling biocontrol property inSynthetic and systems biotechnology · 2026Article
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- Natural Hydroxybenzoic and Hydroxycinnamic Acids Derivatives: Mechanisms of Action and Therapeutic Applications.Antioxidants (Basel, Switzerland) · 2025Review
- Heterologous Expression and Optimization of Fermentation Conditions for Recombinant Ikarugamycin Production.Biotechnology and bioengineering · 2025Article
- A plug-and-play system for polycyclic tetramate macrolactam production and functionalization.Microbial cell factories · 2025Article
- Diversity pattern and antibiotic activity of microbial communities inhabiting a karst cave from Costa Rica.Microbiology (Reading, England) · 2024Article
- Genome sequencing and mining expand the naturalproduct repertoire of Lysobacter.Research square · 2024Article
- Critical analysis of polycyclic tetramate macrolactam biosynthetic gene cluster phylogeny and functional diversity.Applied and environmental microbiology · 2024Article
- A new polycyclic tetramate macrolactam from Allostreptomyces RD068384: stereochemistry and antifungal potential.The Journal of antibiotics · 2024Article
- Old role with new feature: T2SS ATPase as a cyclic-di-GMP receptor to regulate antibiotic production.Applied and environmental microbiology · 2024Article
- Soil bacterium manipulates antifungal weapons by sensing intracellular type IVA secretion system effectors of a competitor.The ISME journal · 2023Article
- Iron ions regulate antifungal HSAF biosynthesis inMicrobiology spectrum · 2023Article
- Quorum quenching by a type IVA secretion system effector.The ISME journal · 2023Article
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- Genetic Basis and Expression Pattern Indicate the Biocontrol Potential and Soil Adaption ofMicroorganisms · 2023Article
- Combating Antimicrobial Resistance in the Post-Genomic Era: Rapid Antibiotic Discovery.Molecules (Basel, Switzerland) · 2023Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A screen for antifungal compounds from Lysobacter enzymogenes strain C3, a bacterial biological control agent of fungal diseases, has previously led to the isolation of heat-stable antifungal factor (HSAF). HSAF exhibits inhibitory activities against a wide range of fungal species and shows a novel mode of antifungal action by disrupting the biosynthesis of a distinct group of sphingolipids. We have now determined the chemical structure of HSAF, which is identical to that of dihydromaltophilin, an antifungal metabolite with a unique macrocyclic lactam system containing a tetramic acid moiety and a 5,5,6-tricyclic skeleton. We have also identified the genetic locus responsible for the biosynthesis of HSAF in strain C3. DNA sequencing of this locus revealed genes for a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS), a sterol desaturase, a ferredoxin reductase, and an arginase. The disruption of the PKS-NRPS gene generated C3 mutants that lost the ability to produce HSAF and to inhibit fungal growth, demonstrating a hybrid PKS-NRPS that catalyzed the biosynthesis of the unique macrolactam system that is found in many biologically active natural products isolated from marine organisms. In addition, we have generated mutants with disrupted sterol desaturase, ferredoxin reductase, and arginase and examined the metabolites produced in these mutants. The work represents the first study of the genetic basis for the biosynthesis of the tetramic acid-containing macrolactams. The elucidation of the chemical structure of HSAF and the identification of the genetic locus for its biosynthesis establish the foundation for future exploitation of this group of compounds as new fungicides or antifungal drugs.
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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.