ArticleAngewandte Chemie (International ed. in English)2021
Genome-Mining-Based Discovery of the Cyclic Peptide Tolypamide and TolF, a Ser/Thr Forward O-Prenyltransferase.
Article in Angewandte Chemie (International ed. in English), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Enzymatic Prenylation of Proteins and Peptides: From Cysteine S-Prenylation to Tryptophan-Selective Biocatalysis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Phosphorylation of peptides by a kinase domain in cyanobactin pathways.Nature communications · 2025Article
- Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532.Journal of natural products · 2025Article
- Chemical diversity of cyanobacterial natural products.Natural product reports · 2025Review
- Biosynthesis of guanidine-containing natural products in cyanobacteria.Journal of industrial microbiology & biotechnology · 2024Review
- Article
- Structure Prediction and Genome Mining-Aided Discovery of the Bacterial C-Terminal Tryptophan Prenyltransferase PalQ.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Promiscuous Enzymes for Residue-Specific Peptide and Protein Late-Stage Functionalization.Chembiochem : a European journal of chemical biology · 2023Review
- Cyanotoxins and Other Bioactive Compounds from the Pasteur Cultures of Cyanobacteria (PCC).Toxins · 2023Review
- Chemoenzymatic Late-Stage Modifications Enable Downstream Click-Mediated Fluorescent Tagging of Peptides.Angewandte Chemie (International ed. in English) · 2023Article
- Emulating nonribosomal peptides with ribosomal biosynthetic strategies.RSC chemical biology · 2023Review
- AgeMTPT, a Catalyst for Peptide N-Terminal Modification.ACS synthetic biology · 2022Article
- Biochemical characterization of a cyanobactin arginine-Chemical communications (Cambridge, England) · 2022Article
- Applying Promiscuous RiPP Enzymes to Peptide BackboneACS chemical biology · 2022Article
- Targeted Large-Scale Genome Mining and Candidate Prioritization for Natural Product Discovery.Marine drugs · 2022Review
- Catalysts for the Enzymatic Lipidation of Peptides.Accounts of chemical research · 2022Review
- Biological Activity and Stability of Aeruginosamides from Cyanobacteria.Marine drugs · 2022Article
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Authors and funding
6 authors at 4 institutions in 4 countries.
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Abstract
Cyanobactins comprise a widespread group of peptide metabolites produced by cyanobacteria that are often diversified by post-translational prenylation. Several enzymes have been identified in cyanobactin biosynthetic pathways that carry out chemically diverse prenylation reactions, representing a resource for the discovery of post-translational alkylating agents. Here, genome mining was used to identify orphan cyanobactin prenyltransferases, leading to the isolation of tolypamide from the freshwater cyanobacterium Tolypothrix sp. The structure of tolypamide was confirmed by spectroscopic methods, degradation, and enzymatic total synthesis. Tolypamide is forward-prenylated on a threonine residue, representing an unprecedented post-translational modification. Biochemical characterization of the cognate enzyme TolF revealed a prenyltransferase with strict selectivity for forward O-prenylation of serine or threonine but with relaxed substrate selectivity for flanking peptide sequences. Since cyanobactin pathways often exhibit exceptionally broad substrate tolerance, these enzymes represent robust tools for synthetic biology.
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