ArticleJournal of the American Chemical Society2015
Evolution of Efficient Modular Polyketide Synthases by Homologous Recombination.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Intra- and inter-biosynthetic gene cluster allelic variation as drivers of chemical diversification in Streptomyces.Essays in biochemistry · 2026Review
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Plug-and-play engineering of modular polyketide synthases.Nature chemical biology · 2025Article
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries.Nature communications · 2023Article
- Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition.Nature communications · 2023Article
- Recent trends in biocatalysis.Chemical Society reviews · 2021Review
- Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase.Nature communications · 2021Article
- Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases.Angewandte Chemie (International ed. in English) · 2020Article
- Bacteria as genetically programmable producers of bioactive natural products.Nature reviews. Chemistry · 2020Review
- Article
- Evolution and Diversity of Assembly-Line Polyketide Synthases.Chemical reviews · 2019Review
- Engineering enzymatic assembly lines to produce new antibiotics.Current opinion in microbiology · 2019Review
- Emulating evolutionary processes to morph aureothin-type modular polyketide synthases and associated oxygenases.Nature communications · 2019Article
- Engineering of Chimeric Polyketide Synthases Using SYNZIP Docking Domains.ACS chemical biology · 2019Article
- Engineering the Substrate Specificity of a Modular Polyketide Synthase for Installation of Consecutive Non-Natural Extender Units.Journal of the American Chemical Society · 2019Article
- Computational structural enzymology methodologies for the study and engineering of fatty acid synthases, polyketide synthases and nonribosomal peptide synthetases.Methods in enzymology · 2019Article
- Development of Transcription Factor-Based Designer Macrolide Biosensors for Metabolic Engineering and Synthetic Biology.ACS synthetic biology · 2018Article
- Diversity oriented biosynthesis via accelerated evolution of modular gene clusters.Nature communications · 2017Article
- A Single Active Site Mutation in the Pikromycin Thioesterase Generates a More Effective Macrocyclization Catalyst.Journal of the American Chemical Society · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The structural scaffolds of many complex natural products are produced by multifunctional type I polyketide synthase (PKS) enzymes that operate as biosynthetic assembly lines. The modular nature of these mega-enzymes presents an opportunity to construct custom biocatalysts built in a lego-like fashion by inserting, deleting, or exchanging native or foreign domains to produce targeted variants of natural polyketides. However, previously engineered PKS enzymes are often impaired resulting in limited production compared to native systems. Here, we show a versatile method for generating and identifying functional chimeric PKS enzymes for synthesizing custom macrolactones and macrolides. PKS genes from the pikromycin and erythromycin pathways were hybridized in Saccharomyces cerevisiae to generate hybrid libraries. We used a 96-well plate format for plasmid purification, transformations, sequencing, protein expression, in vitro reactions and analysis of metabolite formation. Active chimeric enzymes were identified with new functionality. Streptomyces venezuelae strains that expressed these PKS chimeras were capable of producing engineered macrolactones. Furthermore, a macrolactone generated from selected PKS chimeras was fully functionalized into a novel macrolide analogue. This method permits the engineering of PKS pathways as modular building blocks for the production of new antibiotic-like molecules.
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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.