A Natural Diels-Alder Biocatalyst Enables Efficient [4+2] Cycloaddition Under Harsh Reaction Conditions
A Natural Diels-Alder Biocatalyst Enables Efficient [4+2] Cycloaddition Under Harsh Reaction Conditions
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天然 Diels-Alder 生物催化剂可在恶劣的反应条件下实现高效的 [4 2] 环加成反应
DOI：
10.1002/cctc.201901285
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发表时间：
2019
期刊：
影响因子：
4.5
通讯作者：
Marsh C
中科院分区：
文献类型：
--
作者：
Marsh C
碳-碳键的形成在合成化学和生物合成中都是一个基本的转变。酶催化这类反应具有精细的选择性，这通常不能用非生物方法实现，但可能受到高温和有机溶剂存在的不耐性的影响，限制了它们的应用。本文报道了β -桶天然Diels - Alderase AbyU的热力学和动力学稳定性，该酶催化抗菌天然产物abyssomicin C的螺戊酸核心形成，并产生3个新的不对称中心。该酶在高温（高达65℃）和有机溶剂（MeOH， CH3CN和DMSO）和化学变性剂盐酸胍存在下催化[4+2]环加成，表明AbyU作为生物催化剂具有潜在的广泛价值。
Carbon‐carbon bond formation is a fundamental transformation in both synthetic chemistry and biosynthesis. Enzymes catalyze such reactions with exquisite selectivity which often cannot be achieved using non‐biological methods but may suffer from an intolerance of high temperature and the presence of organic solvents limiting their applications. Here we report the thermodynamic and kinetic stability of theβ‐barrel natural Diels‐Alderase AbyU, which catalyzes formation of the spirotetronate core of the antimicrobial natural product abyssomicin C, with creation of 3 new asymmetric centers. This enzyme is shown to catalyze [4+2] cycloadditions at elevated temperature (up to 65 °C), and in the presence of organic solvents (MeOH, CH3CN and DMSO) and the chemical denaturant guanidinium hydrochloride, revealing that AbyU has potential widespread value as a biocatalyst.