ArticleNature communications2017
Diversity oriented biosynthesis via accelerated evolution of modular gene clusters.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Unveiling Aziridine-Containing Natural Products by Genomic and Spectroscopic Approaches.Angewandte Chemie (International ed. in English) · 2026Article
- Plug-and-play engineering of modular polyketide synthases.Nature chemical biology · 2025Article
- Expanding catalytic versatility of modular polyketide synthases for alcohol biosynthesis.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
- 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
- Enzyme Catalysis for Sustainable Value Creation Using Renewable Biobased Resources.Molecules (Basel, Switzerland) · 2024Review
- Seamless site-directed mutagenesis in complex cloned DNA sequences using the RedEx method.Nature protocols · 2024Review
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.Nature communications · 2024Article
- Review
- Characterisation of Modular Polyketide Synthases Designed to Make Pentaene Analogues of Amphotericin B.Molecules (Basel, Switzerland) · 2024Article
- The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin.Biomolecules · 2024Article
- Late-stage diversification of bacterial natural products through biocatalysis.Frontiers in bioengineering and biotechnology · 2024Review
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries.Nature communications · 2023Article
- 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
Corrections and comments
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Authors and funding
32 authors.
Funding
Abstract
Erythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular polyketide synthase multienzymes by an assembly-line process in which each module of enzymes in turn specifies attachment of a particular chemical unit. Although polyketide synthase encoding genes have been successfully engineered to produce novel analogues, the process can be relatively slow, inefficient, and frequently low-yielding. We now describe a method for rapidly recombining polyketide synthase gene clusters to replace, add or remove modules that, with high frequency, generates diverse and highly productive assembly lines. The method is exemplified in the rapamycin biosynthetic gene cluster where, in a single experiment, multiple strains were isolated producing new members of a rapamycin-related family of polyketides. The process mimics, but significantly accelerates, a plausible mechanism of natural evolution for modular polyketide synthases. Detailed sequence analysis of the recombinant genes provides unique insight into the design principles for constructing useful synthetic assembly-line multienzymes.
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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.