ArticleNature communications2020
Efficient rational modification of non-ribosomal peptides by adenylation domain substitution.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- A Practical Guideline to Engineering Nonribosomal Peptide Synthetases.Methods in molecular biology (Clifton, N.J.) · 2023Guideline
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes.Molecules (Basel, Switzerland) · 2026Review
- High-Throughput Engineering and Modification of Non-Ribosomal Peptide Synthetases Based on Golden Gate Assembly.Angewandte Chemie (International ed. in English) · 2025Article
- Protein Engineering of Biosynthetic Enzymes Unlocks Libraries of Bioactive Tilimycin Analogs.ACS catalysis · 2025Article
- Exploring the biosynthetic potential of Korean Actinobacteria for antibacterial metabolite discovery.Journal of microbiology (Seoul, Korea) · 2025Article
- Structural Basis for a Scaffolding Role of the COM Domain in Nonribosomal Peptide Synthetases.Angewandte Chemie (International ed. in English) · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Genomics-Driven Discovery of Plantariitin A, a New Lipopeptide inMolecules (Basel, Switzerland) · 2025Article
- Engineering of acyl ligase domain in non-ribosomal peptide synthetases to change fatty acid moieties of lipopeptides.Communications chemistry · 2025Article
- Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.International journal of molecular sciences · 2024Review
- Natural diversifying evolution of nonribosomal peptide synthetases in a defensive symbiont reveals nonmodular functional constraints.PNAS nexus · 2024Article
- Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.Marine drugs · 2024Review
- Biosynthesis of a clickable pyoverdine via in vivo enzyme engineering of an adenylation domain.Microbial cell factories · 2024Article
- High-throughput reprogramming of an NRPS condensation domain.Nature chemical biology · 2024Article
- Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases.ACS chemical biology · 2024Article
- Metagenomic domain substitution for the high-throughput modification of nonribosomal peptides.Nature chemical biology · 2024Article
- Total substitution and partial modification of the set of non-ribosomal peptide synthetases clusters lead to pyoverdine diversity in theFrontiers in microbiology · 2024Article
- Late-stage diversification of bacterial natural products through biocatalysis.Frontiers in bioengineering and biotechnology · 2024Review
- High-Throughput Engineering of Nonribosomal Extension Modules.ACS chemical biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-ribosomal peptide synthetase (NRPS) enzymes form modular assembly-lines, wherein each module governs the incorporation of a specific monomer into a short peptide product. Modules are comprised of one or more key domains, including adenylation (A) domains, which recognise and activate the monomer substrate; condensation (C) domains, which catalyse amide bond formation; and thiolation (T) domains, which shuttle reaction intermediates between catalytic domains. This arrangement offers prospects for rational peptide modification via substitution of substrate-specifying domains. For over 20 years, it has been considered that C domains play key roles in proof-reading the substrate; a presumption that has greatly complicated rational NRPS redesign. Here we present evidence from both directed and natural evolution studies that any substrate-specifying role for C domains is likely to be the exception rather than the rule, and that novel non-ribosomal peptides can be generated by substitution of A domains alone. We identify permissive A domain recombination boundaries and show that these allow us to efficiently generate modified pyoverdine peptides at high yields. We further demonstrate the transferability of our approach in the PheATE-ProCAT model system originally used to infer C domain substrate specificity, generating modified dipeptide products at yields that are inconsistent with the prevailing dogma.
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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.