Journal
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
Volume 94, Issue 1, Pages 236-243Publisher
WILEY
DOI: 10.1002/jctb.5769
Keywords
Crizotinib; dual-enzyme@CaHPO4 hybrid nanoflowers; chiral alcohol; cascade reaction
Categories
Funding
- National Science Foundation of China [21576062]
- Natural Science Foundation of Zhejiang Province [LY18B060009, LY15B060011]
- Technology Research and Development Program of Hangzhou [20120232B13]
- National Innovation and Entrepreneurship Training Program for Undergraduates [201710346013]
- Scientific Research Innovation Fund for Graduate Students of Hangzhou Normal University
- Research Plan for Sprout Talents in University in Zhejiang Province [2017R423027]
- Program for Innovative Research Team in Chinese University [IRT1231]
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BACKGROUND To develop an environment-friendly approach for the synthesis of (S)-1-(2,6-dichloro-3-fluorophenyl) ethyl alcohol, an intermediate of anti-cancer drug Crizotinib, aldehyde ketone reductase and alcohol dehydrogenase were overexpressed in Escherichia coli Rosetta (DE3) and purified via chromatography. Subsequently, they were co-crystalized with CaHPO4 at 4 degrees C to form dual-enzyme@CaHPO4 hybrid nanoflowers (hNFs) which was then used to catalyze the synthesis of (S)-1-(2,6-dichloro-3-fluorophenyl) ethyl alcohol along with the evaluation of its thermal stability and recycling stability. RESULTS At optimum pH of 7.0, the activities of AKR and ADH confined in the dual-enzyme@CaHPO4 hybrid nanoflowers were 3.3- and 2.1-fold that of the corresponding free one. The thermos-stability of confined enzymes was also significantly improved: both enzymes within the hNFs remained more than 80% of initial activities after incubation at 60 degrees C for 8 h, while free enzymes only retained 20% of initial activities under the same treatment conditions. Moreover, AKR and ADH immobilized with a mole ratio of 3:1 confined in hybrid nanoflowers exhibited the highest catalytic activity for the synthesis of chiral ethyl alcohol with a yield up to 90.8% after 12 h. Besides, the final product (S)-1-(2,6-dichloro-3-fluorophenyl) ethyl alcohol showed a high ee value of 99.99%. Further, the hybrid nanoflowers retained their initial activity after 16 recycling cycles of synthesis reaction. CONCLUSION The dual-enzyme@CaHPO4 hybrid nanoflowers efficiently catalyzed synthesis of the chiral compound (S)-1-(2,6-dichloro-3-fluorophenyl) ethyl alcohol. The method can also be applied to other multi-enzyme systems and facilitate their cascade reactions and substrate channeling. (c) 2018 Society of Chemical Industry
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