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Iterative Catalysis in the Biosynthesis of Mitochondrial Complex II Inhibitors Harzianopyridone and Atpenin B

التفاصيل البيبلوغرافية
العنوان: Iterative Catalysis in the Biosynthesis of Mitochondrial Complex II Inhibitors Harzianopyridone and Atpenin B
المؤلفون: Dan Tan, Masao Ohashi, K. N. Houk, Yi Tang, Daiki Kanayama, William C. Turner, Undramaa Bat-Erdene
المصدر: J Am Chem Soc
Journal of the American Chemical Society, vol 142, iss 19
سنة النشر: 2020
مصطلحات موضوعية: Methyltransferase, Stereochemistry, Pyridones, 010402 general chemistry, Ring (chemistry), 01 natural sciences, Biochemistry, Catalysis, Article, Mixed Function Oxygenases, chemistry.chemical_compound, Colloid and Surface Chemistry, Biosynthesis, Pyridine, Reactivity (chemistry), chemistry.chemical_classification, Biological Products, Molecular Structure, General Chemistry, Methyltransferases, Monooxygenase, 0104 chemical sciences, Enzyme, chemistry, 5.1 Pharmaceuticals, Biocatalysis, Chemical Sciences, Hypocreales, Development of treatments and therapeutic interventions
الوصف: The pentasubstituted pyridine natural products harzianopyridone and atpenins are potent inhibitors of mitochondrial complex II. We identified the pathways of these compounds from their fungal producers and uncovered that the biosynthetic steps require multiple iterative enzymes. In particular, a methyltransferase and a flavin-dependent monooxygenase are used iteratively to introduce C5 and C6 methoxy groups. The pathway unexpectedly requires the installation and removal of an N-methoxy group, which is proposed to be a directing group that tunes the reactivity of the pyridone ring, possibly through the alpha effect.
وصف الملف: application/pdf
تدمد: 1520-5126
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::110a3233c5ad01389bf72af313ab68aa
https://pubmed.ncbi.nlm.nih.gov/32365298
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....110a3233c5ad01389bf72af313ab68aa
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15205126