Chaubey, Asha and Parshad, Rajinder and Koul, Surrinder and Taneja, Subhash C. and Qazi, Ghulam N. (2006) Enantioselectivity modulation through immobilization of Arthrobacter sp. lipase: Kinetic resolution of fluoxetine intermediate. Journal of Molecular Catalysis B: Enzymatic, 42 (1-2). pp. 39-44. ISSN 13811177

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Arthrobacter sp. lipase (ABL, MTCC no. 5125) has been identified for its excellent performance in kinetic resolution of a number of drug intermediates. ABL free enzyme provided product II and V (ee < 95%) from racemic fluoxetine intermediate (I and IV) compared to its cell biomass in naturally immobilized state (ee < 98%). To overcome this problem and obtaining high enantioselectivity (R isomer ee 99%), ABL enzyme was modulated by immobilization using various methods vis-`a-vis substrate modification (Scheme 2). Immobilized enzyme obtained by hydrophobic binding provided 6710–7720 U/g, covalent binding 200 U/g, and sol–gel entrapment 65–110 U/g activity. Substantial improvement in enantioselectivity was obtained using acylates of ethyl 3-hydroxy 3-phenylpropanoate a fluoxetine drug intermediate (R isomer ee from 93 to 99% and E from 43 to 127–473) at 29–45% conversion in fixed time period of 21 h, indicating thereby some change in conformation of ABL immobilized enzyme. The ABL immobilized by covalent binding and sol–gel entrapment has demonstrated reasonable superiority over the free ABL in enantioselectivity as well as over all rate of hydrolysis. Immobilized enzymes prepared by covalent and entrapment methods have shown excellent operational stability and used for 10 cycles without loss in activity and the technique can be upscaled for process development.

Item Type: Article
Subjects: Biological Sciences
Depositing User: Mr. Amit Nargotra
Date Deposited: 28 Dec 2011 08:35
Last Modified: 28 Dec 2011 08:35

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