Life Sciences Institute, University of Michigan, 210 Washtenaw Ave., Ann Arbor, MI 28104, USA.
Department of Medicinal Chemistry, University of Michigan, 428 Church St., Ann Arbor, MI 48109, USA.
Chembiochem. 2020 Sep 1;21(17):2449-2454. doi: 10.1002/cbic.202000004. Epub 2020 May 14.
The fungal indole alkaloids are a unique class of complex molecules that have a characteristic bicyclo[2.2.2]diazaoctane ring and frequently contain a spiro-oxindole moiety. While various strains produce these compounds, an intriguing case involves the formation of individual antipodes by two unique species of fungi in the generation of the potent anticancer agents (+)- and (-)-notoamide A. NotI and NotI' have been characterized as flavin-dependent monooxygenases that catalyze epoxidation and semi-pinacol rearrangement to form the spiro-oxindole center within these molecules. This work elucidates a key step in the biosynthesis of the notoamides and provides an evolutionary hypothesis regarding a common ancestor for production of enantiopure notoamides.
真菌吲哚生物碱是一类独特的复杂分子，具有特征性的双环[2.2.2]二氮杂辛烷环，并且通常含有螺-氧吲哚部分。虽然各种菌株都能产生这些化合物，但一个有趣的情况是，两种独特的真菌物种在生成强效抗癌剂（+）-和（-）-诺托酰胺 A 时会形成单个对映异构体。NotI 和 NotI' 已被鉴定为黄素依赖性单加氧酶，可催化环氧化和半频哪醇重排，从而在这些分子中形成螺-氧吲哚中心。这项工作阐明了诺托酰胺生物合成中的关键步骤，并提供了关于产生对映纯诺托酰胺的共同祖先的进化假说。
