Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase

Handle URI:
http://hdl.handle.net/10754/624996
Title:
Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase
Authors:
Bsharat, Odey; Musa, Musa M.; Vieille, Claire; Oladepo, Sulayman; Takahashi, Masateru; Hamdan, Samir ( 0000-0001-5192-1852 )
Abstract:
Ketones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically enriched alcohols by using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones, in particular, were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacts their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explain how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Bsharat O, Musa MM, Vieille C, Oladepo SA, Takahashi M, et al. (2017) Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase. ChemCatChem 9: 1487–1493. Available: http://dx.doi.org/10.1002/cctc.201601618.
Publisher:
Wiley-Blackwell
Journal:
ChemCatChem
Issue Date:
30-Jan-2017
DOI:
10.1002/cctc.201601618
Type:
Article
ISSN:
1867-3880
Sponsors:
The 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 IN151032.
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1002/cctc.201601618/full
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorBsharat, Odeyen
dc.contributor.authorMusa, Musa M.en
dc.contributor.authorVieille, Claireen
dc.contributor.authorOladepo, Sulaymanen
dc.contributor.authorTakahashi, Masateruen
dc.contributor.authorHamdan, Samiren
dc.date.accessioned2017-06-14T12:04:28Z-
dc.date.available2017-06-14T12:04:28Z-
dc.date.issued2017-01-30en
dc.identifier.citationBsharat O, Musa MM, Vieille C, Oladepo SA, Takahashi M, et al. (2017) Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase. ChemCatChem 9: 1487–1493. Available: http://dx.doi.org/10.1002/cctc.201601618.en
dc.identifier.issn1867-3880en
dc.identifier.doi10.1002/cctc.201601618en
dc.identifier.urihttp://hdl.handle.net/10754/624996-
dc.description.abstractKetones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically enriched alcohols by using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones, in particular, were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacts their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explain how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity.en
dc.description.sponsorshipThe 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 IN151032.en
dc.publisherWiley-Blackwellen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1002/cctc.201601618/fullen
dc.subjectasymmetric catalysisen
dc.subjectenzyme catalysisen
dc.subjectketonesen
dc.subjectmutagenesisen
dc.subjectreductionen
dc.titleAsymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenaseen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalChemCatChemen
dc.contributor.institutionKing Fahd University of Petroleum and Minerals; Chemistry Department; 31261 Dhahran SAUDI ARABIAen
dc.contributor.institutionKing Fahd University of Petroleum and Minerals; Chemistry; Department of Chemistry Building #4 31261 Dhahran SAUDI ARABIAen
dc.contributor.institutionMichigan State University; Department of Microbiology and Molecular Genetics; 48824 East Lansing UNITED STATESen
kaust.authorTakahashi, Masateruen
kaust.authorHamdan, Samiren
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