ArticleMetabolic engineering2023
Boosting titers of engineered triketide and tetraketide synthases to record levels through T7 promoter tuning.
Article in Metabolic engineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- 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
- Skeletal editing via multi-step engineering of a modular polyketide synthase.Nature communications · 2026Article
- Expanding catalytic versatility of modular polyketide synthases for alcohol biosynthesis.Nature chemical biology · 2025Article
- Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.Nature chemical biology · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- 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
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Modular polyketide synthases (PKS's) are promising platforms for the rational engineering of designer polyketides and commodity chemicals, yet their low productivities are a barrier to the practical biosynthesis of these compounds. Previously, we engineered triketide lactone synthases such as Pik167 using the recently updated module definition and showed they generate hundreds of milligrams of product per liter of Escherichia coli K207-3 shake flask culture. As the molar ratio between the 2 polypeptides of Pik167 is highly skewed, we sought to attenuate the strength of the T7 promoter controlling the production of the smaller, better-expressing polypeptide and thereby increase production of the first polypeptide under the control of an unoptimized T7 promoter. Through this strategy, a 1.8-fold boost in titer was obtained. After a further 1.5-fold boost obtained by increasing the propionate concentration in the media from 20 to 80 mM, a record titer of 791 mg L
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