ArticleChemistry & biology2012
Codon randomization for rapid exploration of chemical space in thiopeptide antibiotic variants.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 80 citations in OpenAlex.
- A Framework for the In Vivo Production of Extensively Engineered Thiopeptides.ACS synthetic biology · 2026Article
- De novo design of ribosomally synthesized and post-translationally modified peptides.Nature chemistry · 2025Article
- A Compact Reprogrammed Genetic Code for De Novo Discovery of Proteolytically Stable Thiopeptides.Journal of the American Chemical Society · 2024Article
- An Autocatalytic Peptide Cyclase Improves Fidelity and Yield of Circular Peptides In Vivo and In Vitro.ACS synthetic biology · 2024Article
- Deep Learning-Driven Library Design for theACS central science · 2023Article
- Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides.ACS bio & med chem Au · 2023Review
- De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors.Journal of the American Chemical Society · 2022Article
- Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides.Chemical reviews · 2022Review
- Accurate Models of Substrate Preferences of Post-Translational Modification Enzymes from a Combination of mRNA Display and Deep Learning.ACS central science · 2022Article
- Article
- Thiopeptides: antibiotics with unique chemical structures and diverse biological activities.The Journal of antibiotics · 2021Review
- New developments in RiPP discovery, enzymology and engineering.Natural product reports · 2021Review
- Interception of the Bycroft-Gowland Intermediate in the Enzymatic Macrocyclization of Thiopeptides.Journal of the American Chemical Society · 2020Article
- Substrate Recognition by the Class II Lanthipeptide Synthetase HalM2.ACS chemical biology · 2020Article
- Minimal lactazole scaffold for in vitro thiopeptide bioengineering.Nature communications · 2020Article
- Exploring the Post-translational Enzymology of PaaA by mRNA Display.Journal of the American Chemical Society · 2020Article
- Engineering of Streptomyces lividans for heterologous expression of secondary metabolite gene clusters.Microbial cell factories · 2020Article
- Translation-Targeting RiPPs and Where to Find Them.Frontiers in genetics · 2020Review
- Crossroads of Antibiotic Resistance and Biosynthesis.Journal of molecular biology · 2019Review
- Dehydroamino acids: chemical multi-tools for late-stage diversification.Organic & biomolecular chemistry · 2019Review
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3 authors at 2 institutions in 1 country.
Funding
Abstract
Thiopeptide antibiotics exhibit a profound level of chemical diversity that is installed through cascades of posttranslational modifications on ribosomal peptides. Here, we present a technique to rapidly explore the chemical space of the thiopeptide GE37468 through codon randomization, yielding insights into thiopeptide maturation as well as structure and activity relationships. In this incarnation of the methodology, we randomized seven residues of the prepeptide-coding region, enabling the generation of 133 potential thiopeptide variants. Variant libraries were subsequently queried in two ways. First, high-throughput MALDI-TOF mass spectrometry was applied to colony-level expressions to sample mutants that permitted full maturation of the antibiotic. Second, the activity of producing mutants was detected in an antibiotic overlay assay. In total, 29 of the 133 variants produced mature compound, 12 of which retained antibiotic activity and 1 that had improved activity.
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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.