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  Biocatalysts for the pharmaceutical industry created by structure-guided directed evolution of stereoselective enzymes

Li, G., Wang, J., & Reetz, M. T. (2018). Biocatalysts for the pharmaceutical industry created by structure-guided directed evolution of stereoselective enzymes. Bioorganic & Medicinal Chemistry, 26(7), 1241-1251. doi:10.1016/j.bmc.2017.05.021.

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 Creators:
Li, Guangyue1, 2, Author
Wang, Jianbo1, 2, Author              
Reetz, Manfred T.1, 2, Author              
Affiliations:
1Fachbereich Chemie, Philipps-Universität, Hans-Meerwein-Straße 4, 35032 Marburg, ou_persistent22              
2Research Department Reetz, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445588              

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Free keywords: Directed evolution; Enzymatic transformations; Stereoselectivity; Pharmaceuticals; Saturation mutagenesis
 Abstract: Enzymes have been used for a long time as catalysts in the asymmetric synthesis of chiral intermediates needed in the production of therapeutic drugs. However, this alternative to man-made catalysts has suffered traditionally from distinct limitations, namely the often observed wrong or insufficient enantio- and/or regioselectivity, low activity, narrow substrate range, and insufficient thermostability. With the advent of directed evolution, these problems can be generally solved. The challenge is to develop and apply the most efficient mutagenesis methods which lead to highest-quality mutant libraries requiring minimal screening. Structure-guided saturation mutagenesis and its iterative form have emerged as the method of choice for evolving stereo- and regioselective mutant enzymes needed in the asymmetric synthesis of chiral intermediates. The number of (industrial) applications in the preparation of chiral pharmaceuticals is rapidly increasing. This review features and analyzes typical case studies.

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Language(s): eng - English
 Dates: 2016-12-072017-05-092017-05-112018-04-01
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.bmc.2017.05.021
 Degree: -

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Title: Bioorganic & Medicinal Chemistry
  Other : Bioorg. Med. Chem.
Source Genre: Journal
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Publ. Info: Amsterdam, The Netherlands : Elsevier B. V.
Pages: - Volume / Issue: 26 (7) Sequence Number: - Start / End Page: 1241 - 1251 Identifier: ISSN: 0968-0896
CoNE: https://pure.mpg.de/cone/journals/resource/954925582193