Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation

Handle URI:
http://hdl.handle.net/10754/626409
Title:
Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation
Authors:
Musa, Musa M.; Bsharat, Odey; Karume, Ibrahim; Vieille, Claire; Takahashi, Masateru; Hamdan, Samir ( 0000-0001-5192-1852 )
Abstract:
Here, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single and dual site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Further expanding the size of the substrate binding pocket in the mutant W110A/I86A not only allowed substrates of the single mutants W110A and I86A to be accommodated within the expanded active site, but also expanded the enzyme's substrate range to ketones bearing two sterically demanding groups (bulky-bulky ketones), which are not substrates for TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones using W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference generating the Prelog products most of the time and the anti-Prelog products in a few cases.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Musa MM, Bsharat O, Karume I, Vieille C, Takahashi M, et al. (2017) Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation. European Journal of Organic Chemistry. Available: http://dx.doi.org/10.1002/ejoc.201701351.
Publisher:
Wiley-Blackwell
Journal:
European Journal of Organic Chemistry
Issue Date:
14-Dec-2017
DOI:
10.1002/ejoc.201701351
Type:
Article
ISSN:
1434-193X
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 under project number IN151032. They also acknowledge the supported by baseline research fund to S.M.H. by King Abdullah University of Science and Technology.
Additional Links:
onlinelibrary.wiley.com/doi/10.1002/ejoc.201701351/abstract
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorMusa, Musa M.en
dc.contributor.authorBsharat, Odeyen
dc.contributor.authorKarume, Ibrahimen
dc.contributor.authorVieille, Claireen
dc.contributor.authorTakahashi, Masateruen
dc.contributor.authorHamdan, Samiren
dc.date.accessioned2017-12-21T13:57:04Z-
dc.date.available2017-12-21T13:57:04Z-
dc.date.issued2017-12-14en
dc.identifier.citationMusa MM, Bsharat O, Karume I, Vieille C, Takahashi M, et al. (2017) Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation. European Journal of Organic Chemistry. Available: http://dx.doi.org/10.1002/ejoc.201701351.en
dc.identifier.issn1434-193Xen
dc.identifier.doi10.1002/ejoc.201701351en
dc.identifier.urihttp://hdl.handle.net/10754/626409-
dc.description.abstractHere, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single and dual site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Further expanding the size of the substrate binding pocket in the mutant W110A/I86A not only allowed substrates of the single mutants W110A and I86A to be accommodated within the expanded active site, but also expanded the enzyme's substrate range to ketones bearing two sterically demanding groups (bulky-bulky ketones), which are not substrates for TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones using W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference generating the Prelog products most of the time and the anti-Prelog products in a few cases.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 under project number IN151032. They also acknowledge the supported by baseline research fund to S.M.H. by King Abdullah University of Science and Technology.en
dc.publisherWiley-Blackwellen
dc.relation.urlonlinelibrary.wiley.com/doi/10.1002/ejoc.201701351/abstracten
dc.rightsThis is the peer reviewed version of the following article: Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation, which has been published in final form at http://doi.org/10.1002/ejoc.201701351. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.en
dc.titleExpanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutationen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalEuropean Journal of Organic Chemistryen
dc.eprint.versionPost-printen
dc.contributor.institutionChemistry Department, King Fahd University of Petroleum and Minerals, Dhahran, 31261, KSAen
dc.contributor.institutionDepartment of Microbiology and Molecular Genetics and Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USAen
kaust.authorTakahashi, Masateruen
kaust.authorHamdan, Samiren
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