ArticleApplied and environmental microbiology2011
Molecular basis for mycophenolic acid biosynthesis in Penicillium brevicompactum.
Article in Applied and environmental microbiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 168 citations in OpenAlex.
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- Resistance Gene-Guided Discovery of a Fungal Spirotetramate as an Acetolactate Synthase Inhibitor.Journal of the American Chemical Society · 2025Article
- Enhancing the β-Oxidation-Like Pathway for the Optimal Production of the Immunosuppressant Mycophenolic Acid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tracing the Origin and Evolution of the Fungal Mycophenolic Acid Biosynthesis Pathway.Genome biology and evolution · 2025Article
- Design and Synthesis of Mycophenolic Acid Analogues for Osteosarcoma Cancer Treatment.ACS bio & med chem Au · 2025Article
- Different metabolite profiles across Penicillium roqueforti populations associated with ecological niche specialisation and domestication.IMA fungus · 2024Article
- Identification and Reconstitution of the First Two Enzymatic Steps for the Biosynthesis of Bioactive Meroterpenoids fromMolecules (Basel, Switzerland) · 2024Article
- Coprinolide, a novel antifungal tricyclic polyketide with a rare furanone-fused chromene skeleton isolated from the mushroomJournal of pesticide science · 2024Article
- Methyltransferase Domain-Focused Genome Mining for Fungal Polyketide Synthases.Small methods · 2024Article
- Targeting of Specialized Metabolites Biosynthetic Enzymes to Membranes and Vesicles by Posttranslational Palmitoylation: A Mechanism of Non-Conventional Traffic and Secretion of Fungal Metabolites.International journal of molecular sciences · 2024Review
- PrJournal of fungi (Basel, Switzerland) · 2023Article
- FunARTS, the Fungal bioActive compound Resistant Target Seeker, an exploration engine for target-directed genome mining in fungi.Nucleic acids research · 2023Article
- Titer improvement of mycophenolic acid in the novel producer strain Penicillium arizonense and expression analysis of its biosynthetic genes.BMC microbiology · 2023Article
- Secondary Metabolites Produced by the Blue-Cheese Ripening MoldJournal of fungi (Basel, Switzerland) · 2023Review
- Orthoester formation in fungal meroterpenoid austalide F biosynthesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Computer-aided, resistance gene-guided genome mining for proteasome and HMG-CoA reductase inhibitors.Journal of industrial microbiology & biotechnology · 2023Article
- Late-stage cascade of oxidation reactions during the biosynthesis of oxalicine B inActa pharmaceutica Sinica. B · 2023Article
- Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycophenolic acid (MPA) is the active ingredient in the increasingly important immunosuppressive pharmaceuticals CellCept (Roche) and Myfortic (Novartis). Despite the long history of MPA, the molecular basis for its biosynthesis has remained enigmatic. Here we report the discovery of a polyketide synthase (PKS), MpaC, which we successfully characterized and identified as responsible for MPA production in Penicillium brevicompactum. mpaC resides in what most likely is a 25-kb gene cluster in the genome of Penicillium brevicompactum. The gene cluster was successfully localized by targeting putative resistance genes, in this case an additional copy of the gene encoding IMP dehydrogenase (IMPDH). We report the cloning, sequencing, and the functional characterization of the MPA biosynthesis gene cluster by deletion of the polyketide synthase gene mpaC of P. brevicompactum and bioinformatic analyses. As expected, the gene deletion completely abolished MPA production as well as production of several other metabolites derived from the MPA biosynthesis pathway of P. brevicompactum. Our work sets the stage for engineering the production of MPA and analogues through metabolic engineering.
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