ArticleChemistry & biology2013
Engineering the substrate specificity of the DhbE adenylation domain by yeast cell surface display.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 92 citations in OpenAlex.
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- 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 engineering of biosynthetic assembly lines.Nature chemical biology · 2024Article
- High-throughput reprogramming of an NRPS condensation domain.Nature chemical biology · 2024Article
- High-Throughput Engineering of Nonribosomal Extension Modules.ACS chemical biology · 2023Article
- Engineering Siderophore Biosynthesis and Regulation Pathways to Increase Diversity and Availability.Biomolecules · 2023Review
- A Protein-Engineered, Enhanced Yeast Display Platform for Rapid Evolution of Challenging Targets.ACS synthetic biology · 2021Article
- Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens.Journal of industrial microbiology & biotechnology · 2021Review
- Bacillibactins E and F from a Marine Sponge-AssociatedJournal of natural products · 2021Article
- Lessons learned in engineering interrupted adenylation domains when attempting to create trifunctional enzymes from three independent monofunctional ones.RSC advances · 2020Article
- Bacteria as genetically programmable producers of bioactive natural products.Nature reviews. Chemistry · 2020Review
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- Repurposing Modular Polyketide Synthases and Non-ribosomal Peptide Synthetases for Novel Chemical Biosynthesis.Frontiers in molecular biosciences · 2020Review
- Engineering enzymatic assembly lines to produce new antibiotics.Current opinion in microbiology · 2019Review
- Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code.ACS chemical biology · 2019Article
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.The Journal of biological chemistry · 2018Article
- A Defined and Flexible Pocket Explains Aryl Substrate Promiscuity of the Cahuitamycin Starter Unit-Activating Enzyme CahJ.Chembiochem : a European journal of chemical biology · 2018Article
- Substrate selection of adenylation domains for nonribosomal peptide synthetase (NRPS) in bacillamide C biosynthesis by marine Bacillus atrophaeus C89.Journal of industrial microbiology & biotechnology · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
The adenylation (A) domains of nonribosomal peptide synthetases (NRPSs) activate aryl acids or amino acids to launch their transfer through the NRPS assembly line for the biosynthesis of many medicinally important natural products. In order to expand the substrate pool of NRPSs, we developed a method based on yeast cell surface display to engineer the substrate specificities of the A-domains. We acquired A-domain mutants of DhbE that have 11- and 6-fold increases in k(cat)/K(m) with nonnative substrates 3-hydroxybenzoic acid and 2-aminobenzoic acid, respectively and corresponding 3- and 33-fold decreases in k(cat)/K(m) values with the native substrate 2,3-dihydroxybenzoic acid, resulting in a dramatic switch in substrate specificity of up to 200-fold. Our study demonstrates that yeast display can be used as a high throughput selection platform to reprogram the "nonribosomal code" of A-domains.
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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.