ArticleJournal of industrial microbiology & biotechnology2003
Metabolic engineering of Escherichia coli for improved 6-deoxyerythronolide B production.
Article in Journal of industrial microbiology & biotechnology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 138 citations in OpenAlex.
- Heterologous expression of NRPS and PKS pathways in Escherichia coli: from bottlenecks to biosynthetic platforms.Essays in biochemistry · 2026Review
- Engineered polyketide synthases enable a microbial chassis for recyclable plastics with tunable properties.Nature biotechnology · 2026Article
- Engineering an Extremely Hybrid PKS for Adipic Acid Production.ACS synthetic biology · 2026Article
- 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
- Engineering Polyketide Stereocenters with Ketoreductase Domain Exchanges.Journal of the American Chemical Society · 2025Article
- Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.Nature chemical biology · 2025Article
- Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation.ACS chemical biology · 2025Article
- Directed Evolution of a Macrolide-Sensing Transcription Factor Biosensor for the Detection of Macrolactone Aglycones via "Effector Walking" and Efflux Pump Deletion.Biochemistry · 2025Article
- Distinct Acyl Carrier Protein Docking Sites Help Mediate the Opposite Stereoselectivities of A- and B-type Modular Polyketide Synthase Ketoreductases.Biochemistry · 2025Article
- Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli.Research square · 2025Article
- Mutagenesis Supports AlphaFold Prediction of How Modular Polyketide Synthase Acyl Carrier Proteins Dock With Downstream Ketosynthases.Proteins · 2024Article
- 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
- Engineering of a TetR family transcriptional regulator BkdR enhances heterologous spinosad production inApplied and environmental microbiology · 2024Article
- Biosynthesis of novel non-proteinogenic amino acids β-hydroxyenduracididine and β-methylphenylalanine inFrontiers in bioengineering and biotechnology · 2024Article
- Maximizing Heterologous Expression of Engineered Type I Polyketide Synthases: Investigating Codon Optimization Strategies.ACS synthetic biology · 2023Article
- Expression of blue pigment synthetase a from Streptomyces lavenduale reveals insights on the effects of refactoring biosynthetic megasynthases for heterologous expression in Escherichia coli.Protein expression and purification · 2023Article
- Boosting titers of engineered triketide and tetraketide synthases to record levels through T7 promoter tuning.Metabolic engineering · 2023Article
- Expanding Extender Substrate Selection for Unnatural Polyketide Biosynthesis by Acyltransferase Domain Exchange within a Modular Polyketide Synthase.Journal of the American Chemical Society · 2023Article
- Priming enzymes from the pikromycin synthase reveal how assembly-line ketosynthases catalyze carbon-carbon chemistry.Structure (London, England : 1993) · 2022Article
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Authors and funding
5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Escherichia coli is an attractive candidate as a host for polyketide production and has been engineered to produce the erythromycin precursor polyketide 6-deoxyerythronolide B (6dEB). In order to identify and optimize parameters that affect polyketide production in engineered E. coli, we first investigated the supply of the extender unit ( 2S)-methylmalonyl-CoA via three independent pathways. Expression of the Streptomyces coelicolor malonyl/methylmalonyl-CoA ligase ( matB) pathway in E. coli together with methylmalonate feeding resulted in the accumulation of intracellular methylmalonyl-CoA to as much as 90% of the acyl-CoA pool. Surprisingly, the methylmalonyl-CoA generated from the matB pathway was not converted into 6dEB. In strains expressing either the S. coelicolor propionyl-CoA carboxylase (PCC) pathway or the Propionibacteria shermanii methylmalonyl-CoA mutase/epimerase pathway, methylmalonyl-CoA accumulated up to 30% of the total acyl-CoA pools, and 6dEB was produced; titers were fivefold higher when strains contained the PCC pathway rather than the mutase pathway. When the PCC and mutase pathways were expressed simultaneously, the PCC pathway predominated, as indicated by greater flux of (13)C-propionate into 6dEB through the PCC pathway. To further optimize the E. coli production strain, we improved 6dEB titers by integrating the PCC and mutase pathways into the E. coli chromosome and by expressing the 6-deoxyerythronolide B synthase (DEBS) genes from a stable plasmid system.
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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.