Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes
Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes
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DOI：
10.1002/anie.202000129
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发表时间：
2020-05-11
影响因子：
16.6
通讯作者：
Itoh, Shinobu
中科院分区：
文献类型：
--
作者：
Fujieda, Nobutaka;Ichihashi, Haruna;Itoh, Shinobu
Cupin超家族蛋白（TM 1459）作为具有双链β-桶结构的大分子配体框架通过组氨酸侧链连接到Cu离子。改变TM 1459的第一配位球显示，H52 A和H54 A/H58 A突变体有效地催化硝基烷烃的非对映体和对映体选择性Michael加成反应生成α，β-不饱和酮。此外，计算的底物对接表示C106 N和F104 W单点突变，其分别逆转了H52 A的非对映选择性并进一步提高了H54 A/H58 A的立体选择性。
Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantioselective Michael addition reaction of nitroalkanes to an alpha,beta-unsaturated ketone. Moreover, calculated substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.