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  Manipulating the stereoselectivity of a thermostable alcohol dehydrogenase by directed evolution for efficient asymmetric synthesis of arylpropanols

Dong, Y., Yao, P., Cui, Y., Wu, Q., Zhu, D., Li, G., et al. (2019). Manipulating the stereoselectivity of a thermostable alcohol dehydrogenase by directed evolution for efficient asymmetric synthesis of arylpropanols. Biological Chemistry, 400(3), 313-321. doi:10.1515/hsz-2018-0299.

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 Creators:
Dong, Yijie1, Author
Yao, Peiyuan2, Author
Cui, Yunfeng2, Author
Wu, Qiaqing2, Author
Zhu, Dunming2, Author
Li, Guangyue1, 3, 4, Author           
Reetz, Manfred T.2, 3, 4, Author           
Affiliations:
1State Key Laboratory for Biology of Plant Diseases and Insect Pests/Key Laboratory of Control of Biological Hazard Factors (Plant Origin) for Agri-product Quality and Safety, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100081, China, ou_persistent22              
2National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Center for Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 Xi Qi Dao, Tianjin Airport Economic Area, Tianjin 300308, China, ou_persistent22              
3Research Department Reetz, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445588              
4Department of Chemistry, Philipps University, Hans-Meerwein-Strasse 4, D-35032 Marburg, Germany, ou_persistent22              

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Free keywords: alcohol dehydrogenase; chiral arylpropanol; directed evolution; stereoselectivity
 Abstract: Chiral arylpropanols are valuable components in important pharmaceuticals and fragrances, which is the motivation for previous attempts to prepare these building blocks enantioselectively in asymmetric processes using either enzymes or transition metal catalysts. Thus far, enzymes used in kinetic resolution proved to be best, but several problems prevented ecologically and economically viable processes from being developed. In the present study, directed evolution was applied to the thermostable alcohol dehydrogenase TbSADH in the successful quest to obtain mutants that are effective in the dynamic reductive kinetic resolution (DYRKR) of racemic arylpropanals. Using rac-2-phenyl-1-propanal in a model reaction, (S)- and (R)-selective mutants were evolved which catalyzed DYRKR of this racemic substrate with formation of the respective (S)- and (R)-alcohols in essentially enantiomerically pure form. This was achieved on the basis of an unconventional form of iterative saturation mutagenesis (ISM) at randomization sites lining the binding pocket using a reduced amino acid alphabet. The best mutants were also effective in the DYRKR of several other structurally related racemic aldehydes.

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Language(s): eng - English
 Dates: 2018-06-272018-08-302018-10-012019-02-25
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1515/hsz-2018-0299
 Degree: -

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Title: Biological Chemistry
  Other : Biological Chemistry Hoppe-Seyler (Berlin)
  Abbreviation : Biol Chem Hoppe Seyler
Source Genre: Journal
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Publ. Info: Berlin : W. de Gruyter
Pages: - Volume / Issue: 400 (3) Sequence Number: - Start / End Page: 313 - 321 Identifier: ISSN: 1437-4315
ISSN: 1431-6730
CoNE: https://pure.mpg.de/cone/journals/resource/954927622123