化学
突变
合理设计
催化作用
立体化学
对映选择合成
蛋白质工程
氨基酸
非对映体
酶
生物化学
生物
突变
遗传学
基因
作者
Na Liu,Lian Wu,Jinhui Feng,Xiang Sheng,Jian Li,Xi Chen,Jianjiong Li,Weidong Liu,Jiahai Zhou,Qingping Wu,Dunming Zhu
标识
DOI:10.1002/anie.202017225
摘要
Abstract Amino acid dehydrogenases (AADHs) have shown considerable potential as biocatalysts in the asymmetric synthesis of chiral amino acids. However, compared to the widely studied α‐AADHs, limited knowledge is available about β‐AADHs that enable the synthesis of β‐amino acids. Herein, we report the crystal structures of a l ‐ erythro ‐3,5‐diaminohexanoate dehydrogenase and its variants, the only known member of β‐AADH family. Crystal structure analysis, site‐directed mutagenesis studies and quantum chemical calculations revealed the differences in the substrate binding and catalytic mechanism from α‐AADHs. A number of rationally engineered variants were then obtained with improved activity (by 110–800 times) toward various aliphatic β‐amino acids without an enantioselectivity trade‐off. Two β‐amino acids were prepared by using the outstanding variants with excellent enantioselectivity (>99 % ee ) and high isolated yields (86–87 %). These results provide important insights into the molecular mechanism of 3,5‐DAHDH, and establish a solid foundation for further design of β‐AADHs for the asymmetric synthesis of β‐amino acids.
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