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Open AccessArticle

Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

1
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
2
College of Life Sciences, Zhejiang Sci-Tech Univeristy, Hangzhou 310018, China
3
Grain and Oil Products Quality Inspection Center of Zhejiang Province, Hangzhou 310012, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Stefano Serra
Molecules 2018, 23(12), 3117; https://doi.org/10.3390/molecules23123117
Received: 11 November 2018 / Revised: 25 November 2018 / Accepted: 27 November 2018 / Published: 28 November 2018
(This article belongs to the Special Issue Enzymes, Biocatalysis and Chemical Biology)
The recombinant carbonyl reductase from Rhodococcus erythropolis WZ010 (ReCR) demonstrated strict (S)-stereoselectivity and catalyzed the irreversible reduction of N-Boc-3-piperidone (NBPO) to (S)-N-Boc-3-hydroxypiperidine [(S)-NBHP], a key chiral intermediate in the synthesis of ibrutinib. The NAD(H)-specific enzyme was active within broad ranges of pH and temperature and had remarkable activity in the presence of higher concentration of organic solvents. The amino acid residue at position 54 was critical for the activity and the substitution of Tyr54 to Phe significantly enhanced the catalytic efficiency of ReCR. The kcat/Km values of ReCR Y54F for NBPO, (R/S)-2-octanol, and 2-propanol were 49.17 s−1 mM−1, 56.56 s−1 mM−1, and 20.69 s−1 mM−1, respectively. In addition, the (S)-NBHP yield was as high as 95.92% when whole cells of E. coli overexpressing ReCR variant Y54F catalyzed the asymmetric reduction of 1.5 M NBPO for 12 h in the aqueous/(R/S)-2-octanol biphasic system, demonstrating the great potential of ReCR variant Y54F for practical applications. View Full-Text
Keywords: (S)-N-Boc-3-hydroxypiperidine; carbonyl reductase; asymmetric reduction; rational design; Rhodococcus erythropolis (S)-N-Boc-3-hydroxypiperidine; carbonyl reductase; asymmetric reduction; rational design; Rhodococcus erythropolis
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MDPI and ACS Style

Ying, X.; Zhang, J.; Wang, C.; Huang, M.; Ji, Y.; Cheng, F.; Yu, M.; Wang, Z.; Ying, M. Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine. Molecules 2018, 23, 3117.

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