ArticleCell chemical biology2017
Identification and Characterization of the Sulfazecin Monobactam Biosynthetic Gene Cluster.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 74 citations in OpenAlex.
- Transposon mutagenesis in bacterial natural product discovery.Essays in biochemistry · 2026Review
- BGC-MAC and BGC-MAP: Attention-Based Models for Biosynthetic Gene Cluster Classification and Product Matching.Journal of chemical information and modeling · 2026Article
- Non-canonical thioesterases in bacterial non-ribosomal peptide biosynthesis.The Journal of antibiotics · 2025Review
- Small-molecule strategies to combat antibiotic resistance: mechanisms, modifications, and contemporary approaches.RSC advances · 2025Review
- Teicoplanin Nonribosomal Peptide Synthetase Is Unable to Incorporate Alpha-Ketoacid Building Blocks.Biochemistry · 2025Article
- The structure of the monobactam-producing thioesterase domain of SulM forms a unique complex with the upstream carrier protein domain.bioRxiv : the preprint server for biology · 2024Article
- TheiScience · 2024Article
- Comparative Genome Analyses Provide Insight into the Antimicrobial Activity of EndophyticMicroorganisms · 2024Article
- ReducingAnalytical chemistry · 2023Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- Synthesis of functionalized 2,3-diaminopropionates and their potential for directed monobactam biosynthesis.Chemical science · 2023Article
- Colorimetric Determination of Adenylation Domain Activity in Nonribosomal Peptide Synthetases by Using Chrome Azurol S.Chembiochem : a European journal of chemical biology · 2023Article
- Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains.Current opinion in chemical biology · 2023Review
- Insights into group-specific pattern of secondary metabolite gene cluster inFrontiers in microbiology · 2023Review
- Nonribosomal Peptide Synthesis Definitely Working Out of the Rules.Microorganisms · 2022Review
- Long-term excessive application of KFrontiers in plant science · 2022Article
- Biosynthesis of Ditropolonyl Sulfide, an Antibacterial Compound Produced by Burkholderia cepacia Complex Strain R-12632.Applied and environmental microbiology · 2021Article
- Aflatoxin Biosynthesis, Genetic Regulation, Toxicity, and Control Strategies: A Review.Journal of fungi (Basel, Switzerland) · 2021Review
- Pan-Genome Analysis Reveals Host-Specific Functional Divergences inMicroorganisms · 2021Article
- Efficient rational modification of non-ribosomal peptides by adenylation domain substitution.Nature communications · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The monobactams, exemplified by the natural product sulfazecin, are the only class of β-lactam antibiotics not inactivated by metallo-β-lactamases, which confer bacteria with extended-spectrum β-lactam resistance. We screened a transposon mutagenesis library from Pseudomonas acidophila ATCC 31363 and isolated a sulfazecin-deficient mutant that revealed a gene cluster encoding two non-ribosomal peptide synthetases (NRPSs), a methyltransferase, a sulfotransferase, and a dioxygenase. Three modules and an aberrant C-terminal thioesterase (TE) domain are distributed across the two NRPSs. Biochemical examination of the adenylation (A) domains provided evidence that L-2,3-diaminopropionate, not L-serine as previously thought, is the direct source of the β-lactam ring of sulfazecin. ATP/PPi exchange assay also revealed an unusual substrate selectivity shift of one A domain when expressed with or without the immediately upstream condensation domain. Gene inactivation analysis defined a cluster of 13 open reading frames sufficient for sulfazecin production, precursor synthesis, self-resistance, and regulation. The identification of a key intermediate supported a proposed NRPS-mediated mechanism of sulfazecin biosynthesis and β-lactam ring formation distinct from the nocardicins, another NRPS-derived subclass of monocyclic β-lactam. These findings will serve as the basis for further biosynthetic research and potential engineering of these important antibiotics.
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