7dl0 | pdb_00007dl0
The mutant E310G/A314Y of 3,5-DAHDHcca complex with NADPH
Structural highlights
Publication Abstract from PubMedAmino acid dehydrogenases (AADHs) have shown considerable potential as biocatalysts in the asymmetric synthesis of chiral amino acids. However, compared to the widely studied alpha-AADHs, limited knowledge is available about beta-AADHs that enable the synthesis of beta-amino acids. Herein, we report the crystal structures of a l-erythro-3,5-diaminohexanoate dehydrogenase and its variants, the only known member of beta-AADH family. Crystal structure analysis, site-directed mutagenesis studies and quantum chemical calculations revealed the differences in the substrate binding and catalytic mechanism from alpha-AADHs. A number of rationally engineered variants were then obtained with improved activity (by 110-800 times) toward various aliphatic beta-amino acids without an enantioselectivity trade-off. Two beta-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 beta-AADHs for the asymmetric synthesis of beta-amino acids. Crystal Structures and Catalytic Mechanism of l-erythro-3,5-Diaminohexanoate Dehydrogenase and Rational Engineering for Asymmetric Synthesis of beta-Amino Acids.,Liu N, Wu L, Feng J, Sheng X, Li J, Chen X, Li J, Liu W, Zhou J, Wu Q, Zhu D Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10203-10210. doi:, 10.1002/anie.202017225. Epub 2021 Mar 24. PMID:33624917[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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