ArticleMicrobial cell factories2020
Synthesis of acridone derivatives via heterologous expression of a plant type III polyketide synthase in Escherichia coli.
Article in Microbial cell factories, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 19 citations in OpenAlex.
- Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.Nature chemical biology · 2025Article
- The shikimate pathway: gateway to metabolic diversity.Natural product reports · 2024Review
- Metabolic Engineering and Synthetic Biology Approaches for the Heterologous Production of Aromatic Polyketides.International journal of molecular sciences · 2023Review
- Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms.Frontiers in bioengineering and biotechnology · 2022Review
- FermentativeMicroorganisms · 2020Article
- Phytochemical and Therapeutic Potential ofJournal of evidence-based integrative medicineReview
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAcridone alkaloids are heterocyclic compounds that exhibit a broad-range of pharmaceutical and chemotherapeutic activities, including anticancer, antiviral, anti-inflammatory, antimalarial, and antimicrobial effects. Certain plant species such as Citrus microcarpa, Ruta graveolens, and Toddaliopsis bremekampii synthesize acridone alkaloids from anthranilate and malonyl-CoA.
resultsWe synthesized two acridones in Escherichia coli. Acridone synthase (ACS) and anthraniloyl-CoA ligase genes were transformed into E. coli, and the synthesis of acridone was examined. To increase the levels of endogenous anthranilate, we tested several constructs expressing proteins involved in the shikimate pathway and selected the best construct. To boost the supply of malonyl-CoA, genes coding for acetyl-coenzyme A carboxylase (ACC) from Photorhabdus luminescens were overexpressed in E. coli. For the synthesis of 1,3-dihydroxy-10-methylacridone, we utilized an N-methyltransferase gene (NMT) to supply N-methylanthranilate and a new N-methylanthraniloyl-CoA ligase. After selecting the best combination of genes, approximately 17.3 mg/L of 1,3-dihydroxy-9(10H)-acridone (DHA) and 26.0 mg/L of 1,3-dihydroxy-10-methylacridone (NMA) were synthesized.
conclusionsTwo bioactive acridone derivatives were synthesized by expressing type III plant polyketide synthases and other genes in E. coli, which increased the supplement of substrates. This study showed that is possible to synthesize diverse polyketides in E. coli using plant polyketide synthases.
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