Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.
Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.
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DOI：
10.1038/nchembio.2283
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发表时间：
2017-03
影响因子：
14.8
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Zou Y;Garcia-Borràs M;Tang MC;Hirayama Y;Li DH;Li L;Watanabe K;Houk KN;Tang Y
环氧化合物是在全合成和生物合成过程中构建复杂天然产物的重要合成物和生物合成物。在酶催化的环氧化物转化中，与合成工具箱相比，一个明显缺失的反应是在强酸下发生的阳离子重排。对于酶催化来说，这是一个具有挑战性的转变，因为需要在环氧化物裂解时稳定碳正离子中间体。在这里，我们发现了两种Brønsted酸性酶，它们可以催化生物学中前所未有的两种环氧化物转化。戊喹诺酮途径的PenF在生理条件下催化阳离子环氧化物重排生成季碳中心，而阿斯喹诺酮途径的AsqO在生理条件下催化3-外环烷环化生成环丙烷-四氢呋喃环体系。这些新的环氧化合物修饰酶的发现进一步突出了环氧化合物在天然产物生物合成过程中产生复杂性的多功能性。
Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.