ArticleScience advances2015
Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously engineered in E. coli.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Metabolic engineering approaches for the biosynthesis of antibiotics.Microbial cell factories · 2025Review
- Marine Macrolides to Tackle Antimicrobial Resistance ofMarine drugs · 2022Review
- Multi-strategy engineering unusual sugar TDP-l-mycarose biosynthesis to improve the production of 3-Synthetic and systems biotechnology · 2022Article
- Docking-guided rational engineering of a macrolide glycosyltransferase glycodiversifies epothilone B.Communications biology · 2022Article
- Complex natural product production methods and options.Synthetic and systems biotechnology · 2021Review
- ActDES - a curated Actinobacterial Database for Evolutionary Studies.Microbial genomics · 2021Article
- GDP-Mannose 3,5-Epimerase: A View on Structure, Mechanism, and Industrial Potential.Frontiers in molecular biosciences · 2021Review
- Crossroads of Antibiotic Resistance and Biosynthesis.Journal of molecular biology · 2019Review
- Engineering actinomycetes for biosynthesis of macrolactone polyketides.Microbial cell factories · 2019Review
- Recent advances in the discovery and combinatorial biosynthesis of microbial 14-membered macrolides and macrolactones.Journal of industrial microbiology & biotechnology · 2019Review
- Broadened glycosylation patterning of heterologously produced erythromycin.Biotechnology and bioengineering · 2018Article
- Toward Light-Regulated Living Biomaterials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- Applications of Yeast Synthetic Biology Geared towards the Production of Biopharmaceuticals.Genes · 2018Review
- Heterologous erythromycin production across strain and plasmid construction.Biotechnology progress · 2018Article
- Engineering Heterologous Production of Salicylate Glucoside and Glycosylated Variants.Frontiers in microbiology · 2018Article
- Natural products as reservoirs of novel therapeutic agents.EXCLI journal · 2018Review
- Production of the polyketide 6-deoxyerythronolide B in the heterologous host Bacillus subtilis.Applied microbiology and biotechnology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I modular polyketide synthases are responsible for potent therapeutic compounds that include avermectin (antihelinthic), rapamycin (immunosuppressant), pikromycin (antibiotic), and erythromycin (antibiotic). However, compound access and biosynthetic manipulation are often complicated by properties of native production organisms, prompting an approach (termed heterologous biosynthesis) illustrated in this study through the reconstitution of the erythromycin pathway through Escherichia coli. Using this heterologous system, 16 tailoring pathways were introduced, systematically producing eight chiral pairs of deoxysugar substrates. Successful analog formation for each new pathway emphasizes the remarkable flexibility of downstream enzymes to accommodate molecular variation. Furthermore, analogs resulting from three of the pathways demonstrated bioactivity against an erythromycin-resistant Bacillus subtilis strain. The approach and results support a platform for continued molecular diversification of the tailoring components of this and other complex natural product pathways in a manner that mirrors the modular nature of the upstream megasynthases responsible for aglycone polyketide formation.
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