ArticleAngewandte Chemie (International ed. in English)2014
Reprogramming nonribosomal peptide synthetases for "clickable" amino acids.
Article in Angewandte Chemie (International ed. in English), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 124 citations in OpenAlex.
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- Adenylation Domain Engineering Enables Biosynthesis of an Improved Polymyxin Antibiotic.Angewandte Chemie (International ed. in English) · 2026Article
- Generative AI designs functional thiolation domains for reprogramming non-ribosomal peptide synthetases.Nature communications · 2026Article
- Structure of a stand-alone homodimeric nonribosomal peptide synthetase condensation domain reveals occlusion of the canonical carrier-protein interface.The Journal of biological chemistry · 2026Article
- Mapping the nonribosomal specificity code through promiscuity-guided A-domain engineering.Chemical science · 2026Article
- Structure of a Stand-Alone Homodimeric NRPS Condensation Domain Reveals Occlusion of the Canonical Carrier-Protein Interface.bioRxiv : the preprint server for biology · 2026Article
- Exploring the Substrate Flexibility of GrsB Thioesterase Leads to the Structural Reassignment of a Gramicidin S Variant.Chembiochem : a European journal of chemical biology · 2025Article
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- Article
- Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.International journal of molecular sciences · 2024Review
- 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
- Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains.Natural product reports · 2024Review
- High-throughput reprogramming of an NRPS condensation domain.Nature chemical biology · 2024Article
- Mutagenetic analysis of the biosynthetic pathway of tetramate bripiodionen bearing 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton.Microbial cell factories · 2024Article
- Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases.ACS chemical biology · 2024Article
- High-Throughput Engineering of Nonribosomal Extension Modules.ACS chemical biology · 2023Article
- Repurposing conformational changes in ANL superfamily enzymes to rapidly generate biosensors for organic and amino acids.Nature communications · 2023Article
- Multiplexed Assessment of Promiscuous Non-Canonical Amino Acid Synthase Activity in a Pyridoxal Phosphate-Dependent Protein Family.ACS catalysis · 2023Article
- Biosynthetic incorporation of fluorinated amino acids into the nonribosomal peptide gramicidin S.RSC chemical biology · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonribosomal peptide synthetases (NRPSs) are multifunctional enzymes that produce a wide array of bioactive peptides. Here we show that a single tryptophan-to-serine mutation in phenylalanine-specific NRPS adenylation domains enables the efficient activation of non-natural aromatic amino acids functionalized with azide and alkyne groups. The resulting 10(5)-fold switch in substrate specificity was achieved without appreciable loss of catalytic efficiency. Moreover, the effective communication of the modified A domains with downstream modules in dipeptide synthetases permitted incorporation of O-propargyl-L-tyrosine into diketopiperazines both in vitro and in vivo, even in the presence of competing phenylalanine. Because azides and alkynes readily undergo bioorthogonal click reactions, reprogramming NRPSs to accept non-natural amino acids that contain these groups provides a potentially powerful means of isolating, labeling, and modifying biologically active peptides.
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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.