Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Environmental Science and Engineering Program
King Abdullah University of Science and Technology; Biological and Environmental Science and Engineering; SAUDI ARABIA
Laboratory of DNA Replication and Recombination
Online Publication Date2020-07-16
Print Publication Date2020-08-16
Embargo End Date2021-07-03
Permanent link to this recordhttp://hdl.handle.net/10754/664114
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AbstractWe developed a one-pot two-step deracemization approach for alcohols using two mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase ( Te SADH). This approach relies on consecutive non-stereospecific oxidation of alcohols and stereoselective reduction of their prochiral ketones using two mutants of Te SADH with poor and good stereoselectivities, respectively. More specifically, W110G Te SADH enables a non-stereospecific oxidation of alcohol racemates to their corresponding prochiral ketones, followed by W110V Te SADH-catalyzed stereoselective reduction of the resultant ketone intermediates to enantiopure ( S )-configured alcohols in up to >99% enantiomeric excess. A heat treatment after the oxidation step was required to avoid the interference of the marginally stereoselective W110G Te SADH in the reduction step; this heat treatment was eliminated by using sol-gel encapsulated W110G Te SADH in the oxidation step. Moreover, this bi-enzymatic approach was implemented in the stereoinversion of ( R )-configured alcohols, and ( S )-configured alcohols with up to >99% enantiomeric excess were obtained by this Mitsunobu-like stereoinversion reaction.
CitationNafiu, S. A., Takahashi, M., Takahashi, E., Hamdan, S. M., & Musa, M. M. (2020). Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus. European Journal of Organic Chemistry. doi:10.1002/ejoc.202000728
SponsorsThe authors acknowledge the support provided by the Deanship of Scientific Research (DSR) at King Fahd University of Petroleum and Minerals (KFUPM) for funding this work through project number DF191007. The authors also thank Prof. Claire Vieille, from the Department of Microbiology and Molecular Genetics as well as Biochemistry and Molecular Biology at Michigan State University, for providing the plasmids of TeSADH.