ArticleNature metabolism2023
Improved polyketide production in C. glutamicum by preventing propionate-induced growth inhibition.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Engineering of Corynebacterium glutamicum for biosynthesis of the pharmaceutically active N-acetyltyramine: establishing and optimizing de novo production.Journal of biological engineering · 2026Article
- Balancing Cell Growth and Product Synthesis for Efficient Microbial Cell Factories.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.Nature chemical biology · 2025Article
- Fast growth and high-titer bioproduction from renewable formate via metal-dependent formate dehydrogenase in Escherichia coli.Nature communications · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Comprehensive evaluation of the capacities of microbial cell factories.Nature communications · 2025Article
- Metabolic engineering approaches for the biosynthesis of antibiotics.Microbial cell factories · 2025Review
- Engineering of a TetR family transcriptional regulator BkdR enhances heterologous spinosad production inApplied and environmental microbiology · 2024Article
- Engineered cytosine base editor enabling broad-scope and high-fidelity gene editing in Streptomyces.Nature communications · 2024Article
- Designing a highly efficient type III polyketide whole-cell catalyst with minimized byproduct formation.Biotechnology for biofuels and bioproducts · 2024Article
- Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast.Nature communications · 2024Article
- Application of functional genomics for domestication of novel non-model microbes.Journal of industrial microbiology & biotechnology · 2024Review
- Maximizing Heterologous Expression of Engineered Type I Polyketide Synthases: Investigating Codon Optimization Strategies.ACS synthetic biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Corynebacterium glutamicum is a promising host for production of valuable polyketides. Propionate addition, a strategy known to increase polyketide production by increasing intracellular methylmalonyl-CoA availability, causes growth inhibition in C. glutamicum. The mechanism of this inhibition was unclear before our work. Here we provide evidence that accumulation of propionyl-CoA and methylmalonyl-CoA induces growth inhibition in C. glutamicum. We then show that growth inhibition can be relieved by introducing methylmalonyl-CoA-dependent polyketide synthases. With germicidin as an example, we used adaptive laboratory evolution to leverage the fitness advantage of polyketide production in the presence of propionate to evolve improved germicidin production. Whole-genome sequencing revealed mutations in germicidin synthase, which improved germicidin titer, as well as mutations in citrate synthase, which effectively evolved the native glyoxylate pathway to a new methylcitrate pathway. Together, our results show that C. glutamicum is a capable host for polyketide production and we can take advantage of propionate growth inhibition to drive titers higher using laboratory evolution or to screen for production of polyketides.
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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.