ArticleNature chemical biology2014
Epimerization and substrate gating by a TE domain in β-lactam antibiotic biosynthesis.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 63 citations in OpenAlex.
- Reprogramming the enduracidin NRPS assembly line via thioesterase domain relocation.Synthetic and systems biotechnology · 2027Article
- Investigating the P450-Mediated Cross-Linking of the Atypical GPA Complestatin Using Alternate Peptide Probes.The Journal of organic chemistry · 2026Article
- 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
- Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.International journal of molecular sciences · 2024Review
- Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation.ACS catalysis · 2024Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- Structural Studies of Modular Nonribosomal Peptide Synthetases.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Nonribosomal Peptide Synthesis Definitely Working Out of the Rules.Microorganisms · 2022Review
- Exploring the Molecular Basis of Substrate and Product Selectivities of Nocardicin Bifunctional Thioesterase.Interdisciplinary sciences, computational life sciences · 2022Article
- Acyl Donor Stringency and Dehydroaminoacyl Intermediates in β-Lactam Formation by a Non-ribosomal Peptide Synthetase.ACS chemical biology · 2021Article
- Evolutionary and functional analysis of an NRPS condensation domain integrates β-lactam, ᴅ-amino acid, and dehydroamino acid synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359.Nature communications · 2021Article
- CariogenicACS infectious diseases · 2020Article
- Structure of a bound peptide phosphonate reveals the mechanism of nocardicin bifunctional thioesterase epimerase-hydrolase half-reactions.Nature communications · 2019Article
- The hidden enzymology of bacterial natural product biosynthesis.Nature reviews. Chemistry · 2019Article
- Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.Cell chemical biology · 2019Article
- Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation.Nature communications · 2018Article
- Mechanism of Integrated β-Lactam Formation by a Nonribosomal Peptide Synthetase during Antibiotic Synthesis.Biochemistry · 2018Article
- Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase.Nature chemical biology · 2018Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Nonribosomal peptide synthetases are versatile engines of bioactive natural product biosynthesis that function according to the multiple carrier thiotemplate mechanism. C-terminal thioesterase (TE) domains of these giant modular proteins typically catalyze product release by hydrolysis or macrocyclization. We now report an unprecedented, dual-function TE that is involved in the biosynthesis of nocardicin A, which is the paradigm monocyclic β-lactam antibiotic. Contrary to our expectation, a stereodefined series of potential peptide substrates for the nocardicin TE domain failed to undergo hydrolysis. The stringent discrimination against peptide intermediates was overcome by prior monocyclic β-lactam formation at an L-seryl site. Kinetic data are interpreted such that the TE domain acts as a gatekeeper to hold the assembling peptide on an upstream domain until β-lactam formation takes place and then rapidly catalyzes epimerization, which has not been observed previously as a TE catalytic function, and thioesterase cleavage to discharge a fully fledged pentapeptide β-lactam harboring nocardicin G, the universal precursor of the nocardicins.
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