ArticleProceedings of the National Academy of Sciences of the United States of America2020
Reconstitution of polythioamide antibiotic backbone formation reveals unusual thiotemplated assembly strategy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Biosynthesis of 6-thioguanine: characterizing two intermediates involved in its thioamide formation reaction.ACS catalysis · 2026Article
- Article
- Decarboxylation in Natural Products Biosynthesis.JACS Au · 2024Review
- Cell-Free Systems: Ideal Platforms for Accelerating the Discovery and Production of Peptide-Based Antibiotics.International journal of molecular sciences · 2024Review
- The shikimate pathway: gateway to metabolic diversity.Natural product reports · 2024Review
- The many facets of sulfur incorporation in natural product biosynthesis.Current opinion in chemical biology · 2023Review
- Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides inAntibiotics (Basel, Switzerland) · 2022Article
- Understanding and Circumventing the Requirement for Native Thioester Substrates for α-Oxoamine Synthase Reactions.ACS chemical biology · 2022Article
- A Specialized Polythioamide-Binding Protein Confers Antibiotic Self-Resistance in Anaerobic Bacteria.Angewandte Chemie (International ed. in English) · 2022Article
- Substrate Recognition by the Peptidyl-(ACS chemical biology · 2022Article
- Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them.Antibiotics (Basel, Switzerland) · 2022Review
- Mining and unearthing hidden biosynthetic potential.Nature communications · 2021Review
- Glycine-derived nitronates bifurcate to O-methylation or denitrification in bacteria.Nature chemistry · 2021Article
- Enzyme-Primed Native Chemical Ligation Produces Autoinducing Cyclopeptides in Clostridia.Angewandte Chemie (International ed. in English) · 2021Article
- An Unexpected Split-Merge Pathway in the Assembly of the Symmetric Nonribosomal Peptide Antibiotic Closthioamide.Angewandte Chemie (International ed. in English) · 2021Article
- Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism.mBio · 2020Article
- Sulfur incorporation into biomolecules: recent advances.Critical reviews in biochemistry and molecular biologyReview
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4 authors.
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Abstract
Closthioamide (CTA) is a rare example of a thioamide-containing nonribosomal peptide and is one of only a handful of secondary metabolites described from obligately anaerobic bacteria. Although the biosynthetic gene cluster responsible for CTA production and the thioamide synthetase that catalyzes sulfur incorporation were recently discovered, the logic for peptide backbone assembly has remained a mystery. Here, through the use of in vitro biochemical assays, we demonstrate that the amide backbone of CTA is assembled in an unusual thiotemplated pathway involving the cooperation of a transacylating member of the papain-like cysteine protease family and an iteratively acting ATP-grasp protein. Using the ATP-grasp protein as a bioinformatic handle, we identified hundreds of such thiotemplated yet nonribosomal peptide synthetase (NRPS)-independent biosynthetic gene clusters across diverse bacterial phyla. The data presented herein not only clarify the pathway for the biosynthesis of CTA, but also provide a foundation for the discovery of additional secondary metabolites produced by noncanonical biosynthetic pathways.
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