ArticleNature communications2021
In vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Atypical Condensation Domains Guide Discovery and Illuminate Biosynthesis of Myxoglucamides Featuring Vinyl-Substituted, α-Oxidized γ-Amino Acids.Angewandte Chemie (International ed. in English) · 2026Article
- Unveiling the Taxonomic Diversity and Unprecedented Biosynthetic Treasure of the Phylum Myxococcota.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural basis for iterative methylation by a cobalamin-dependent radicalProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural Basis for Iterative Methylation by a Cobalamin-dependent Radical S-Adenosylmethionine Enzyme in Cystobactamids Biosynthesis.bioRxiv : the preprint server for biology · 2025Article
- Radical Fluoromethylation Enabled by Cobalamin-Dependent Radical SAM Enzymes.ACS bio & med chem Au · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- YgiV promoter mutations cause resistance to cystobactamids and reduced virulence factor expression in Escherichia coli.npj antimicrobials and resistance · 2024Article
- Harnessing Gram-negative bacteria for novel anti-Gram-negative antibiotics.Microbial biotechnology · 2024Review
- In Vitro Activity of Two Novel Antimicrobial Compounds on MDR-Resistant Clinical Isolates.Antibiotics (Basel, Switzerland) · 2023Article
- Genetic manipulation and tools in myxobacteria for the exploitation of secondary metabolism.Engineering microbiology · 2023Review
- Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials.EMBO reports · 2023Review
- Redirecting RiPP Biosynthetic Enzymes to Proteins and Backbone-Modified Substrates.ACS central science · 2022Article
- Nonribosomal Peptide Synthesis Definitely Working Out of the Rules.Microorganisms · 2022Review
- Lapcin, a potent dual topoisomerase I/II inhibitor discovered by soil metagenome guided total chemical synthesis.Nature communications · 2022Article
- Biotechnological production optimization of argyrins - a potent immunomodulatory natural product class.Microbial biotechnology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystobactamids are myxobacteria-derived topoisomerase inhibitors with potent anti-Gram-negative activity. They are formed by a non-ribosomal peptide synthetase (NRPS) and consist of tailored para-aminobenzoic acids, connected by a unique α-methoxy-L-isoasparagine or a β-methoxy-L-asparagine linker moiety. We describe the heterologous expression of the cystobactamid biosynthetic gene cluster (BGC) in Myxococcus xanthus. Targeted gene deletions produce several unnatural cystobactamids. Using in vitro experiments, we reconstitute the key biosynthetic steps of linker formation and shuttling via CysB to the NRPS. The biosynthetic logic involves a previously uncharacterized bifunctional domain found in the stand-alone NRPS module CysH, albicidin biosynthesis and numerous BGCs of unknown natural products. This domain performs either an aminomutase (AM) or an amide dehydratase (DH) type of reaction, depending on the activity of CysJ which hydroxylates CysH-bound L-asparagine. Furthermore, CysQ O-methylates hydroxyl-L-(iso)asparagine only in the presence of the AMDH domain. Taken together, these findings provide direct evidence for unique steps in cystobactamid biosynthesis.
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