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A Catalyst from Burkholderia cenocepacia for Efficient Anti-Prelog’s Bioreduction of 3,5-Bis(Trifluoromethyl) Acetophenone

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Abstract

(R)-3, 5-Bis(trifluoromethyl)phenyl ethanol is a key chiral intermediate for the synthesis of aprepitant. Through a genome mining approach, an NADPH-dependent short-chain dehydrogenases derived from Burkholderia cenocepacia (Bc-SDR) was discovered with excellent anti-Prelog’s stereoselectivity of reducing 3, 5-bis(trifluoromethyl) acetophenone. The enzyme with 247 amino acids was successfully expressed in Escherichia coli and the molecular weight was about 26 kDa. Optimization of reaction conditions showed that the optimum temperature and pH of the enzyme was 25 °C and pH 7.0, respectively. Strong enhancement of enzyme activity was observed in the presence of 1 mM Mn2+. In addition, Bc-SDR exhibited (R)-selective enantioselectivity toward acetophenone derivatives, which makes it a potential catalyst for obtaining aromatic chiral alcohols as useful blocks in pharmaceutical applications.

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Author notes

  1. Songzhu Yu and Hongxia Li contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of China

    Songzhu Yu, Hongxia Li, Yan Lu & Guojun Zheng

Authors
  1. Songzhu Yu
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  2. Hongxia Li
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  3. Yan Lu
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  4. Guojun Zheng
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Correspondence to Guojun Zheng.

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Electronic supplementary material

ESM 1

Fig. S1 Multiple sequence alignment of the target sequence (NCBI Reference Sequence: ANZ75577.1, ANZ77886.1, ANZ77893.1, XP_002489352.1, XP_002492297.1, XP_002493760.1, XP_002494195.1, WP_006481546.1, WP_006481604.1, WP_006481801.1, WP_006483065.1, WP_006485075.1, WP_006485158.1, WP_006488202.1, WP_012336650.1, WP_012492403.1, WP_050013528.1, WP_058903664.1, WP_060214413.1, WP_077189930.1) with the template sequence (Leifsonia xyli HS0904) Fig. S2 Sequence alignment of the target sequence (Burkholderia cenocepacia) with the template sequence (Leifsonia xyli HS0904). (DOCX 9094 kb)

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Yu, S., Li, H., Lu, Y. et al. A Catalyst from Burkholderia cenocepacia for Efficient Anti-Prelog’s Bioreduction of 3,5-Bis(Trifluoromethyl) Acetophenone. Appl Biochem Biotechnol 184, 1319–1331 (2018). https://doi.org/10.1007/s12010-017-2628-8

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  • DOI: https://doi.org/10.1007/s12010-017-2628-8

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