ArticleProceedings of the National Academy of Sciences of the United States of America1999
A multiplasmid approach to preparing large libraries of polyketides.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 148 citations in OpenAlex.
- Establishing Selectivity Trends with Reactions of Thioesterases and Semi-Synthetic Polyketides.Journal of the American Chemical Society · 2025Article
- Review
- Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases.Angewandte Chemie (International ed. in English) · 2020Article
- Challenges and opportunities for engineering assembly-line polyketide biosynthesis inMetabolic engineering communications · 2020Article
- An in vitro platform for engineering and harnessing modular polyketide synthases.Nature communications · 2020Article
- Liposome fragment-mediated introduction of multiple plasmids intoBiochemistry and biophysics reports · 2019Article
- Development of a cyanobacterial heterologous polyketide production platform.Metabolic engineering · 2018Article
- Discovery of the leinamycin family of natural products by mining actinobacterial genomes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Identification of a Thioesterase Bottleneck in the Pikromycin Pathway through Full-Module Processing of Unnatural Pentaketides.Journal of the American Chemical Society · 2017Article
- A Single Active Site Mutation in the Pikromycin Thioesterase Generates a More Effective Macrocyclization Catalyst.Journal of the American Chemical Society · 2017Article
- Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects.Molecules (Basel, Switzerland) · 2017Review
- Multiplexed integrating plasmids for engineering of the erythromycin gene cluster for expression in Streptomyces spp. and combinatorial biosynthesis.Applied and environmental microbiology · 2015Article
- Modification of rifamycin polyketide backbone leads to improved drug activity against rifampicin-resistant Mycobacterium tuberculosis.The Journal of biological chemistry · 2014Article
- Importance of microbial natural products and the need to revitalize their discovery.Journal of industrial microbiology & biotechnology · 2014Review
- Sequence, cloning, and analysis of the fluvirucin B1 polyketide synthase from Actinomadura vulgaris.ACS synthetic biology · 2013Article
- Heterologous expression and manipulation of three tetracycline biosynthetic pathways.Angewandte Chemie (International ed. in English) · 2012Article
- A mechanism-based fluorescence transfer assay for examining ketosynthase selectivity.Organic & biomolecular chemistry · 2012Article
- Biochemical and structural characterization of germicidin synthase: analysis of a type III polyketide synthase that employs acyl-ACP as a starter unit donor.Journal of the American Chemical Society · 2012Article
- Artificial chromosomes to explore and to exploit biosynthetic capabilities of actinomycetes.Journal of biomedicine & biotechnology · 2012Review
- Dissecting complex polyketide biosynthesis.Computational and structural biotechnology journal · 2012Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A three-plasmid system for heterologous expression of 6-deoxyerythronolide B synthase (DEBS) has been developed to facilitate combinatorial biosynthesis of polyketides made by type I modular polyketide synthases (PKSs). The eryA PKS genes encoding the three DEBS subunits were individually cloned into three compatible Streptomyces vectors carrying mutually selectable antibiotic resistance markers. A strain of Streptomyces lividans transformed with all three plasmids produced 6-deoxyerythronolide B at a level similar to that of a strain transformed with a single plasmid containing all three genes. The utility of this system in combinatorial biosynthesis was demonstrated through production of a library of modified polyketide macrolactones by using versions of each plasmid constructed to contain defined mutations. Combinations of these vector sets were introduced into S. lividans, resulting in strains producing a wide range of 6-deoxyerythronolide B analogs. This method can be extended to any modular PKS and has the potential to produce thousands of novel natural products, including ones derived from further modification of the PKS products by tailoring enzymes.
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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.