ArticleAngewandte Chemie (International ed. in English)2023
Reshaping the 2-Pyrone Synthase Active Site for Chemoselective Biosynthesis of Polyketides.
Article in Angewandte Chemie (International ed. in English), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- A case study of evolutionary variability and determinism among type III polyketide synthases.Nature communications · 2026Article
- Harnessing Photoenzymatic Systems for Intermolecular C-H Fluorination.Angewandte Chemie (International ed. in English) · 2026Article
- Production of triacetic acid lactone from oleic acid by engineering the yeast Candida viswanathii.Microbial cell factories · 2025Article
- Creating novel metabolic pathways by protein engineering for bioproduction.Trends in biotechnology · 2025Review
- Recent advances in genetic engineering and chemical production in yeast species.FEMS yeast research · 2025Review
- Biosynthesis-Guided Discovery and Engineering of α-Pyrone Natural Products from Type I Polyketide Synthases.ACS chemical biology · 2023Article
- Reshaping the 2-Pyrone Synthase Active Site for Chemoselective Biosynthesis of Polyketides.Angewandte Chemie (International ed. in English) · 2023Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Engineering enzymes with novel reactivity and applying them in metabolic pathways to produce valuable products are quite challenging due to the intrinsic complexity of metabolic networks and the need for high in vivo catalytic efficiency. Triacetic acid lactone (TAL), naturally generated by 2-pyrone synthase (2PS), is a platform molecule that can be produced via microbial fermentation and further converted into value-added products. However, these conversions require extra synthetic steps under harsh conditions. We herein report a biocatalytic system for direct generation of TAL derivatives under mild conditions with controlled chemoselectivity by rationally engineering the 2PS active site and then rewiring the biocatalytic pathway in the metabolic network of E. coli to produce high-value products, such as kavalactone precursors, with yields up to 17 mg/L culture. Computer modeling indicates sterics and hydrogen-bond interactions play key roles in tuning the selectivity, efficiency and yield.
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Registered trials
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