Efficient Biocatalytic Synthesis of Chiral Intermediate of Pregabalin Using Immobilized Talaromyces thermophilus Lipase.

A mutant L206F/P207F/L259F of Talaromyces thermophilus lipase (TTL) exhibited high hydrolytic activity towards 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) for synthesis of (S)-2-carboxyethyl-3-cyano-5-methylhexanoic acid (S-CCMA), a key chiral intermediate of pregabalin. However,...

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Publicado en:BioMed Research International pp. 1 - 8
Autores principales: Ding, Xu, Tang, Xiao-Ling, Zheng, Ren-Chao, Zheng, Yu-Guo
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 11/1/2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 11/1/2018
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        132770527
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        10.1155/2018/6192059
        132770527
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        atl: Efficient Biocatalytic Synthesis of Chiral Intermediate of Pregabalin Using Immobilized Talaromyces thermophilus Lipase.
      aug:
        au:
          Ding, Xu
          Tang, Xiao-Ling
          Zheng, Ren-Chao
          Zheng, Yu-Guo
        affil: Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
      sug:
        subj:
          Chemistry, Pharmaceutical
          Pregabalin Analogs and Derivatives
          Enzymes Metabolism
          Fungi
          Lipase
          Esterification
          Mycological Typing Techniques
          Resins
          Biotechnology Methods
      ab: A mutant L206F/P207F/L259F of Talaromyces thermophilus lipase (TTL) exhibited high hydrolytic activity towards 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) for synthesis of (S)-2-carboxyethyl-3-cyano-5-methylhexanoic acid (S-CCMA), a key chiral intermediate of pregabalin. However, low conversion at high CNDE concentration and unreusability of the free TTL mutant restricted its industrial applications. In this study, the TTL mutant was immobilized onto epoxy resin and its catalytic properties for kinetic resolution of CNDE were investigated. Under the optimized conditions, the immobilized lipase exhibited an increased catalytic efficiency even at a CNDE concentration of 3 M with 49.7% conversion and 95% eep. The conversion retained higher than 46.3% even after 10 times repeated use of the immobilized lipase in n-heptane-water biphasic system. These results demonstrated great potential of the immobilized TTL mutant for industrial production of the chiral intermediate of pregabalin.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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