Simultaneous cyclic deracemisation and stereoinversion of alcohols using orthogonal biocatalytic oxidation and reduction reactions
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Laboratory of DNA Replication and Recombination
Embargo End Date2022-01-03
Permanent link to this recordhttp://hdl.handle.net/10754/668160
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AbstractWe developed a concurrent cyclic deracemisation approach for secondary alcohols that combines a non-stereospecific oxidation step and a stereoselective reduction step using two mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH) that exhibit various extents of stereoselectivities. In this approach, W110G TeSADH, a sparingly stereoselective mutant, performs the non-stereospecific oxidation step and W110V/G198D TeSADH performs the stereoselective reduction step. The use of orthogonal cofactor regeneration systems allowed for the spontaneous operation of these mutants. (S)-Configured alcohols were obtained in moderate ee's from their racemates using this strategy. To our knowledge, this report provides the first example of a fully enzymatic cyclic deracemisation with a stereoselective reduction step (CD-RS) for alcohols. This approach was further improved into a deracemisation strategy via stereoinversion using concurrent (R)-selective I86A TeSADH-catalysed oxidation that leaves (S)-alcohols untouched and W110V/G198D TeSADH-catalysed stereoselective reduction of the resultant ketone intermediates into the corresponding (S)-configured alcohols. The latter strategy enabled quantitative production of (S)-1-phenylethanol in >99% ee from its racemate. Overall, we show the superiority of the stereoinversion deracemisation approach for alcohols when compared with cyclic deracemisation, which is mainly due to the elimination of futile cycles in the former.
CitationNafiu, S. A., Takahashi, M., Takahashi, E., Hamdan, S. M., & Musa, M. M. (2020). Simultaneous cyclic deracemisation and stereoinversion of alcohols using orthogonal biocatalytic oxidation and reduction reactions. Catalysis Science & Technology, 10(24), 8213–8218. doi:10.1039/d0cy01524e
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 acknowledge the baseline funding of Prof. Hamdan (KAUST) for constructing the TeSADH mutants. 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.
PublisherRoyal Society of Chemistry (RSC)
JournalCatalysis Science and Technology