3082-62-0Relevant articles and documents
Iterative Alanine Scanning Mutagenesis Confers Aromatic Ketone Specificity and Activity of L-Amine Dehydrogenases
Mu, Xiaoqing,Wu, Tao,Mao, Yong,Zhao, Yilei,Xu, Yan,Nie, Yao
, p. 5243 - 5253 (2021/11/16)
Direct reductive amination of prochiral ketones catalyzed by amine dehydrogenases is attractive in the synthesis of active pharmaceutical ingredients. Here, we report the protein engineering of L-Bacillus cereus amine dehydrogenase to allow reactivity on synthetically useful aromatic ketone substrates using an iterative, multiple-site alanine scanning mutagenesis approach. Mutagenesis libraries based on molecular docking, iterative alanine scanning, and double-proximity filter approach significantly expand the scope of active pharmaceutical ingredients relevant building blocks. The eventual quintuple mutant (A115G/T136A/L42A/V296A/V293A) showed reactivity toward aromatic ketones 12 a (5-phenyl-pentan-2-one) and 13 a (6-phenyl-hexan-2-one), which have not been reported to serve as targets of reductive amination by currently available amine dehydrogenases. Docking simulation and tunnel analysis provided valuable insights into the source of the acquired specificity and activity.
Air Stable Iridium Catalysts for Direct Reductive Amination of Ketones
Polishchuk, Iuliia,Sklyaruk, Jan,Lebedev, Yury,Rueping, Magnus
supporting information, p. 5919 - 5922 (2021/03/08)
Half-sandwich iridium complexes bearing bidentate urea-phosphorus ligands were found to catalyze the direct reductive amination of aromatic and aliphatic ketones under mild conditions at 0.5 mol % loading with high selectivity towards primary amines. One of the complexes was found to be active in both the Leuckart–Wallach (NH4CO2H) type reaction as well as in the hydrogenative (H2/NH4AcO) reductive amination. The protocol with ammonium formate does not require an inert atmosphere, dry solvents, as well as additives and in contrast to previous reports takes place in hexafluoroisopropanol (HFIP) instead of methanol. Applying NH4CO2D or D2 resulted in a high degree of deuterium incorporation into the primary amine α-position.
Thermal and Mechanical Stability of Immobilized Candida antarctica Lipase B: an Approximation to Mechanochemical Energetics in Enzyme Catalysis.
Pérez-Venegas, Mario,Tellez-Cruz, Miriam M.,Solorza-Feria, Omar,López-Munguía, Agustín,Castillo, Edmundo,Juaristi, Eusebio
, p. 803 - 811 (2019/12/11)
Very recently, several successful enzymatic processes performed with mechanical activation have been disclosed; that is, despite the mechanical stress caused by High-Speed Ball-Milling, immobilized enzymes can retain activity. In the present study, the effect of thermal and mechanical stress was examined as potential inducers of enzymatic denaturation, when using either free, immobilized, or ground immobilized enzyme. The recorded observations show a remarkable stability of ground immobilized enzyme. Moreover, ground biocatalyst turns out to exhibit an increase of one order of magnitude in the efficiency of the catalytic process, maintaining excellent enantiodiscrimination, without significant activity loss even after four milling cycles. These observations rule out enzyme inactivation as direct consequence of the milling process. Additionally, boosted enzyme efficiency was used to optimize a relatively inefficient chiral amine resolution reaction, achieving a 25 % faster biotransformation (in 45 min) and yielding essentially enantiopure products (ee>99%, E>500).