ArticleNature communications2019
Emulating evolutionary processes to morph aureothin-type modular polyketide synthases and associated oxygenases.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Engineered Modular Polyketide Synthases Elucidate How Enoylreductases Collaborate with Downstream Acyl Carrier Proteins and Ketosynthases to Set Stereocenters.Journal of the American Chemical Society · 2026Article
- Skeletal editing via multi-step engineering of a modular polyketide synthase.Nature communications · 2026Article
- Article
- Diverse chemotypes of polyketides as promising antimicrobial agents: latest progress.RSC advances · 2025Review
- Plug-and-play engineering of modular polyketide synthases.Nature chemical biology · 2025Article
- Gene conversion-associated successive engineering of modular polyketide synthases.Communications chemistry · 2025Article
- Ancestral sequence reconstruction as a tool for structural analysis of modular polyketide synthases.Nature communications · 2025Article
- Mixing and Matching of Hybrid Megasynthases is a Hub for the Evolution of Metabolic Diversity in Cyanobacteria.Angewandte Chemie (International ed. in English) · 2025Article
- A CRISPR-Cas9 system for knock-out and knock-in of high molecular weight DNA enables module-swapping of the pikromycin synthase in its native host.Microbial cell factories · 2025Article
- Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli.Research square · 2025Article
- Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad inSynthetic and systems biotechnology · 2024Article
- Mutagenesis Supports AlphaFold Prediction of How Modular Polyketide Synthase Acyl Carrier Proteins Dock With Downstream Ketosynthases.Proteins · 2024Article
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Modular polyketide synthase ketosynthases collaborate with upstream dehydratases to install double bonds.Chemical communications (Cambridge, England) · 2024Article
- Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.Nature communications · 2024Article
- Evolution-guided engineering ofScience (New York, N.Y.) · 2024Article
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Enzymology of assembly line synthesis by modular polyketide synthases.Nature chemical biology · 2023Review
- Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition.Nature communications · 2023Article
- Engineering the stambomycin modular polyketide synthase yields 37-membered mini-stambomycins.Nature communications · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyketides produced by modular type I polyketide synthases (PKSs) play eminent roles in the development of medicines. Yet, the production of structural analogs by genetic engineering poses a major challenge. We report an evolution-guided morphing of modular PKSs inspired by recombination processes that lead to structural diversity in nature. By deletion and insertion of PKS modules we interconvert the assembly lines for related antibiotic and antifungal agents, aureothin (aur) and neoaureothin (nor) (aka spectinabilin), in both directions. Mutational and functional analyses of the polyketide-tailoring cytochrome P450 monooxygenases, and PKS phylogenies give contradictory clues on potential evolutionary scenarios (generalist-to-specialist enzyme evolution vs. most parsimonious ancestor). The KS-AT linker proves to be well suited as fusion site for both excision and insertion of modules, which supports a model for alternative module boundaries in some PKS systems. This study teaches important lessons on the evolution of PKSs, which may guide future engineering approaches.
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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.