179237-92-4Relevant articles and documents
Substrate binding to Candida tenuis xylose reductase during catalysis
Vogl, Michael,Brecker, Lothar
, p. 25997 - 26004 (2013)
Candida tenuis xylose reductase (CtXR) is studied by in situ NMR, saturation transfer difference (STD) NMR, and molecular docking with respect to its substrate and coenzyme binding in ternary complexes. The natural substrate Xyl as well as Glc and methyl-glucosides preferentially bind as α-anomers of the pyranose forms. These α-anomers are transformed faster, predominately leading to STD effects in the formed products, and can be better docked into the CtXR active site than the β-anomer. The reduction is initiated by α-Xylp ring opening prior to hydride transfer from NADH. Binding and transformation of unnatural 2,4-dichloroacetophenone is not as good, although it is reduced with very high catalytic efficiency. STD NMR indicates a reasonable amount to leave the ternary complex in unreduced form. The molecular docking calculation confirms this result, as only a couple of the investigated ternary complexes allow reduction of the substrates.
Biocatalytic preparation of a key intermediate of antifungal drugs using an alcohol dehydrogenase with high organic tolerance
Yan, Jinrong,Wang, Xiaojing,Li, Fangling,Yang, Lei,Shi, Guixiang,Sun, Weihang,Shao, Lei,Huang, Junhai,Wu, Kai
supporting information, (2021/10/20)
In this study, an alcohol dehydrogenase derived from Lactobacillus kefir (LkADH) was engineered and a simple and practical bioreduction system was developed for the preparation of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CDPO), a key intermediate for the synthesis of antifungal drugs. Through active pocket iterative saturation mutagenesis, mutant LkADH-D18 (Y190C/V196L/M206H/D150H) was obtained with high stereoselectivity (99% ee, R vs 87% ee, S) and increased activity (0.44 μmol·min?1·mg?1). LkADH-D18 demonstrated NAD(P)H regeneration capability using a high concentration of isopropanol (IPA) as a co-substrate. Using 40% IPA (v/v), 400 mM of (R)-CDPO (90.1 g·L-1) was obtained via complete substrate conversion using 40 mg·mL?1 LkADH-D18 wet cells. The biocatalytic process catalyzed at constant pH with the cheap co-solvent IPA contributed to improved isolated yield of (R)-CDPO (97%), lower reaction cost, and simpler downstream purification, indicating the potential utility of LkADH-D18 in future industrial applications.
Optimisation, scope and advantages of the synthesis of chiral phenylethanols using whole seeds of Bauhinia variegata L. (Fabaceae) as a new and stereoselective bio-reducer of carbonyl compounds
Aimar, Mario L.,Bordón, Daniela L.,Cantero, Juan J.,Decarlini, María F.,Demmel, Gabriela I.,Rossi, Laura I.,Ruiz, Gustavo M.,Vázquez, Ana M.
, p. 1 - 15 (2020/07/14)
With the aim of finding new methods for environmentally friendly synthesis of chiral phenylethanols, a screening was carried out to identify seeds that could be used as a biocatalyst capable of reducing stereoselectively prochiral ketones. As a result, seeds of Bauhinia variegata L. (Fabaceae) were identified as being an efficient and stereoselective biological reducer of acetophenone to produce (S)-1-phenylethanol (conversion of 98% and 99 e.e.%). Then, to optimise the reductive process, the effects of some variables such as temperature, load of substrate, pH, co-solvent, and reuse and storability of the seeds as a function of time were established. Utilising the optimal reaction conditions, nineteen substituted acetophenones were reduced to their corresponding chiral alcohols with a conversion ranging from 30% to 98% and enantiomeric excess of between 65% and >99%, and in addition, useful key intermediates were also obtained by the synthesis of drugs. The scope and advantages of this new biocatalytic synthetic method are also discussed.Research highlights A screening was carried out to identify seeds that could be used as a biocatalyst Seeds of Bauhinia variegata have been identified as an efficient biocatalyst to reduce carbonyl compounds. Acetophenone and substituted acetophenones were reduced with high stereoselectivity. Some key intermediates were synthetised using this methodology. Seeds can be stored for twenty-four months without loss of activity.
