ArticleNature2016
Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed.
- Systematic Categorization and Functional Diversity of Secondary Metabolites from Bacillus spp.: A Review.Probiotics and antimicrobial proteins · 2026Review
- The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes.Molecules (Basel, Switzerland) · 2026Review
- A new gut pathogenic bacteria and its metabolites promote colorectal cancer development and act as non-invasive early diagnostic biomarkers.Gut microbes · 2025Article
- Structural Basis for a Scaffolding Role of the COM Domain in Nonribosomal Peptide Synthetases.Angewandte Chemie (International ed. in English) · 2025Article
- Enzyme-mediated aminoglycoside resistance without target mimicry.Communications chemistry · 2025Article
- Mixing and Matching of Hybrid Megasynthases is a Hub for the Evolution of Metabolic Diversity in Cyanobacteria.Angewandte Chemie (International ed. in English) · 2025Article
- Whole-genome sequencing and comparative genomic analysis ofMicrobial genomics · 2025Article
- Teicoplanin Nonribosomal Peptide Synthetase Is Unable to Incorporate Alpha-Ketoacid Building Blocks.Biochemistry · 2025Article
- Animal-Encoded Nonribosomal Pathway to Bursatellin Analogs.Journal of the American Chemical Society · 2025Article
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- Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains.Natural product reports · 2024Review
- The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain.Science advances · 2024Article
- Subdomain dynamics enable chemical chain reactions in non-ribosomal peptide synthetases.Nature chemistry · 2024Article
- High-Throughput Engineering of Nonribosomal Extension Modules.ACS chemical biology · 2023Article
- Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides.Nature communications · 2023Article
- Repurposing conformational changes in ANL superfamily enzymes to rapidly generate biosensors for organic and amino acids.Nature communications · 2023Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- Classification and Multifaceted Potential of Secondary Metabolites Produced byMolecules (Basel, Switzerland) · 2023Review
- Structural Studies of Modular Nonribosomal Peptide Synthetases.Methods in molecular biology (Clifton, N.J.) · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Nonribosomal peptide synthetases (NRPSs) are very large proteins that produce small peptide molecules with wide-ranging biological activities, including environmentally friendly chemicals and many widely used therapeutics. NRPSs are macromolecular machines, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. In addition to the core domains required to link the substrates, they often include specialized tailoring domains, which introduce chemical modifications and allow the product to access a large expanse of chemical space. It is still unknown how the NRPS tailoring domains are structurally accommodated into megaenzymes or how they have adapted to function in nonribosomal peptide synthesis. Here we present a series of crystal structures of the initiation module of an antibiotic-producing NRPS, linear gramicidin synthetase. This module includes the specialized tailoring formylation domain, and states are captured that represent every major step of the assembly-line synthesis in the initiation module. The transitions between conformations are large in scale, with both the peptidyl carrier protein domain and the adenylation subdomain undergoing huge movements to transport substrate between distal active sites. The structures highlight the great versatility of NRPSs, as small domains repurpose and recycle their limited interfaces to interact with their various binding partners. Understanding tailoring domains is important if NRPSs are to be utilized in the production of novel therapeutics.
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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.