The crystal structure of the S154Y mutant carbonyl reductase from Leifsonia xyli explains enhanced activity for 3,5-bis(trifluoromethyl)acetophenone reduction

Structural analysis of an anthrol reductase inspires enantioselective synthesis of enantiopure hydroxycycloketones and β-halohydrins

“…3b, c ), which will determine the stereo- and regioselectivity of the reaction due to the direction of nucleophilic attack of the hydrogen atoms at the C4 position on the pyridine ring of NADPH to the carbonyl oxygen of emodin (Fig. 3b, c ) 35 . Thus, we conclude that residues Asn152, His162 and Tyr210 play critical roles in recognition, binding and stabilization of emodin.…”

Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

“…The structure showed the effective interaction of the two trifluoromethyl groups with Tyr 157 in the active site and facilitated the reduction reaction, wherein no such interaction was observed in the wild type enzyme. 99…”

“…The structure showed the effective interaction of the two trifluoromethyl groups with Tyr 157 in the active site and facilitated the reduction reaction, wherein no such interaction was observed in the wild type enzyme. 99 A concurrent series of reactions involving gold(I) N-heterocyclic carbene and overexpressed alcohol dehydrogen-ase were carried out under environmentally benign conditions to produce enantiopure halohydrins. The methodology involved the regioselective hydration of haloalkynes followed by bioreduction of the corresponding α-halomethyl ketones using 2-propanol as the hydrogen donor.…”

Engineering ketoreductases for the enantioselective synthesis of chiral alcohols

“…S154Y-LxCAR, produced by replacing Ser154 by Tyr154 afforded 28a in 83% yield and 99.4% ee at 256 g L À1 substrate loading by establishing extra noncovalent contacts with trifluoromethyl groups. 104 The asymmetric synthesis of (R)-28b from 28a also proceeded smoothly in whole cells expressing a fusion protein of LkCR (carbonyl reductase from Lactobacillus kefir), discovered by genome data mining, and BsGDH (GDH from Bacillus subtilis) by using 10 nm rigid linker peptides with helical ER/K motifs (Scheme 13B). 105 Rivastigmine [(S)-3-[1-(dimethylamino)-ethyl]phenyl ethyl-(methyl)carbamate] 31 is an oral acetylcholinesterase inhibitor used for treatment of Alzheimer disease.…”