Wang, Dong-Hao published the artcileAsymmetric Reductive Amination of Structurally Diverse Ketones with Ammonia Using a Spectrum-Extended Amine Dehydrogenase, Application of Ethyl 4-oxopentanoate, the main research area is asym reductive amination reductive engineered amine dehydrogenase.
Amine dehydrogenase-catalyzed reductive amination of prochiral ketones with ammonia is a promising method for the synthesis of optically pure amines in the pharmaceutical and fine chem. industries. However, previously reported amine dehydrogenases show restricted catalytic capacity toward bulky ketones, which limits their widespread applications toward the production of chiral amines. Herein, we expanded the substrate scope of an engineered amine dehydrogenase GkAmDH from Geobacillus kaustophilus via laboratory evolution for the reductive amination of an extensive set of ketones. Several beneficial mutants were identified with a up to 2.2 U mg-1 activity toward bulky benzylacetone, 110-fold higher than that of M0. Using the engineered M3 and M8, structurally diverse bulky chiral amines could be synthesized with up to >99% conversion, >99% ee, and up to 18,900 TON. Among them, two key chiral intermediates used in the synthesis of the drugs medroxalol and dilevalol were produced on a gram scale in up to 85% yield and >99% ee. Addnl., the engineered enzymes M3 and M8 displayed considerable thermostability with a half-life of more than three days at 50 °C. These results demonstrate that these engineered amine dehydrogenases are promising biocatalysts for the synthesis of chiral amines. Mol. dynamics simulations provide insights into how mutations improve the amination activity toward bulky ketones and the thermostability.
ACS Catalysis published new progress about Directed evolution. 539-88-8 belongs to class esters-buliding-blocks, name is Ethyl 4-oxopentanoate, and the molecular formula is C7H12O3, Application of Ethyl 4-oxopentanoate.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics