ArticleNature chemical biology2025
Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Metabolic engineering of Escherichia coli for methanol-assisted resveratrol biosynthesis.Bioprocess and biosystems engineering · 2026Article
- Biosynthesis and Microbial Production of Carminic Acid: From Pathway Elucidation to Synthetic Biology.Microorganisms · 2026Review
- Toward Complex Polyketide Biosynthesis inJournal of microbiology and biotechnology · 2026Review
- Optimizing MatB-MatC-Dependent Malonyl-CoA Supply for Enhanced Raspberry Ketone Production inBiotech (Basel (Switzerland)) · 2026Article
- 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
- Engineering an Acyl-CoA Ligase With Enhanced Activity Toward Synthetic CoA Alternatives.Chembiochem : a European journal of chemical biology · 2026Article
- Toward sustainable food preservatives: high-level production of sorbic acid in engineered Saccharomyces cerevisiae.Nature communications · 2026Article
- De novo biosynthesis of alpinetin enhanced by directed evolution of 5-O-methyltransferase.Microbial cell factories · 2026Article
- Alternative malonyl-CoA pathways for microbial production of diverse products.Applied microbiology and biotechnology · 2026Review
- Metabolic engineering of Escherichia coli for resveratrol production using food-grade D-xylose as a carbon source.Journal of industrial microbiology & biotechnology · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Heterologous expression of polyketide synthase (PKS) genes in Escherichia coli has enabled the production of various valuable natural and synthetic products. However, the limited availability of malonyl-CoA (M-CoA) in E. coli remains a substantial impediment to high-titer polyketide production. Here we address this limitation by disrupting the native M-CoA biosynthetic pathway and introducing an orthogonal pathway comprising a malonate transporter and M-CoA ligase, enabling efficient M-CoA biosynthesis under malonate supplementation. This approach substantially increases M-CoA levels, enhancing fatty acid and polyketide titers while reducing the promiscuous activity of PKSs toward undesired acyl-CoA substrates. Subsequent adaptive laboratory evolution of these strains provides insights into M-CoA regulation and identifies mutations that further boost M-CoA and polyketide production. This strategy improves E. coli as a host for polyketide biosynthesis and advances understanding of M-CoA metabolism in microbial systems.
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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.