ArticleNature communications2021
Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Dissection and Engineering of Modular Polyketide Synthase Extender Unit Specificity Motifs.Chembiochem : a European journal of chemical biology · 2026Article
- Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026Review
- Graph neural networks can predict ketosynthase substrate specificity.Scientific reports · 2026Article
- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Evolutionary Reprogramming of Acyltransferase Domains in Polyene Macrolide Pathways.Microorganisms · 2026Article
- Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation.Marine drugs · 2025Review
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Directed Evolution of a Macrolide-Sensing Transcription Factor Biosensor for the Detection of Macrolactone Aglycones via "Effector Walking" and Efflux Pump Deletion.Biochemistry · 2025Article
- Repurposing a Fully Reducing Polyketide Synthase toward 2-Methyl Guerbet-like Lipids.ACS catalysis · 2024Article
- Engineering of a Malonyl-CoA Ligase for Production of Fluorinated Polyketide Extender Units.Chembiochem : a European journal of chemical biology · 2024Article
- The malonyl/acetyl-transferase from murine fatty acid synthase is a promiscuous engineering tool for editing polyketide scaffolds.Communications chemistry · 2024Article
- Investigation of chain-length selection by the tenellin iterative highly-reducing polyketide synthase.RSC advances · 2024Article
- Discrete Acyltransferases and Thioesterases in Iso-Migrastatin and Lactimidomycin Biosynthesis.Biochemistry · 2024Article
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products.Chembiochem : a European journal of chemical biology · 2023Review
- Biosynthesis-Guided Discovery and Engineering of α-Pyrone Natural Products from Type I Polyketide Synthases.ACS chemical biology · 2023Article
- Expanding Extender Substrate Selection for Unnatural Polyketide Biosynthesis by Acyltransferase Domain Exchange within a Modular Polyketide Synthase.Journal of the American Chemical Society · 2023Article
- Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition.Nature communications · 2023Article
- Endowing homodimeric carbamoyltransferase GdmN with iterative functions through structural characterization and mechanistic studies.Nature communications · 2022Article
- Targeted Enzyme Modifications Enable Regioselective Biosynthesis of Fluorinated Polyketides.Chem catalysis · 2022Article
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Authors and funding
7 authors.
Funding
Abstract
Polyketides, one of the largest classes of natural products, are often clinically relevant. The ability to engineer polyketide biosynthesis to produce analogs is critically important. Acyltransferases (ATs) of modular polyketide synthases (PKSs) catalyze the installation of malonyl-CoA extenders into polyketide scaffolds. ATs have been targeted extensively to site-selectively introduce various extenders into polyketides. Yet, a complete inventory of AT residues responsible for substrate selection has not been established, limiting the scope of AT engineering. Here, molecular dynamics simulations are used to prioritize ~50 mutations within the active site of EryAT6 from erythromycin biosynthesis, leading to identification of two previously unexplored structural motifs. Exchanging both motifs with those from ATs with alternative extender specificities provides chimeric PKS modules with expanded and inverted substrate specificity. Our enhanced understanding of AT substrate selectivity and application of this motif-swapping strategy are expected to advance our ability to engineer PKSs towards designer polyketides.
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