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Preparation of Interface-Assembled Carbonyl Reductase and Its Application in the Synthesis of S-Licarbazepine in Toluene/Tris-HCl Buffer Biphasic System

  • Ou, Zhimin (Pharmaceuticals College, Zhejiang University of Technology) ;
  • Xu, Jiahui (Pharmaceuticals College, Zhejiang University of Technology) ;
  • Du, Lihua (Pharmaceuticals College, Zhejiang University of Technology) ;
  • Tang, Lan (Pharmaceuticals College, Zhejiang University of Technology) ;
  • Niu, Yangping (Linan People's Hospital) ;
  • Cui, Jian (Linan People's Hospital)
  • Received : 2017.11.20
  • Accepted : 2018.02.06
  • Published : 2018.04.28

Abstract

In this study, interface-assembled carbonyl reductase (IACR) was prepared and used in the synthesis of S-licarbazepine in a toluene/Tris-HCl biphasic system. The carbonyl reductase (CR) was conjugated with polystyrene to form a surfactant-like structure at the interface of the toluene/Tris-HCl biphasic system. The interface-assembled efficiency of IACR reached 83% when the CR (180 U/mg) and polystyrene concentration were $8{\times}10^2g/ml$ and $3.75{\times}10^3g/ml$, respectively. The conversion reached 95.6% and the enantiometric excess of S-licarbazepine was 98.6% when $3.97{\times}10^6nmol/l$ oxcarbazepine was converted by IACR using 6% ethanol as a co-substrate in toluene/Tris-HCl (12.5:10) at $30^{\circ}C$ and $43{\times}g$ for 6 h. IACR could be reused efficiently five times.

Keywords

References

  1. Biton V, Rogin JB, Krauss G, Aboukhalil B, Rocha JF, Moreira J, et al. 2017. Adjunctive eslicarbazepine acetate: a pooled analysis of three phase III trials. Epilepsy Behav. 72: 127-134. https://doi.org/10.1016/j.yebeh.2017.04.019
  2. Servais AC, Janicot B, Takam A, Crommen J, Fillet M. 2016. Liquid chromatography separation of the chiral prodrug eslicarbazepine acetate and its main metabolites in polar organic mode. Application to their analysis after in vitro metabolism. J. Chromatogr. A 1467: 306-311. https://doi.org/10.1016/j.chroma.2016.07.022
  3. Modukuru NK, Sukumaran J, Steven J, Chan AS, Gohel A. 2014. Development of a practical, biocatalytic reduction for the manufacture of S-licarbazepine using an evolved ketoreductase. Org. Process Res. Dev. 18: 810-815. https://doi.org/10.1021/op4003483
  4. Ou ZM, Shi HB, Sun XY, Shen WH. 2011. Synthesis of S-licarbazepine by asymmetric reduction of oxcarbazepine with Saccharomyces cerevisiae CGMCC No. 2266. J. Mol. Catal. B Enzyme 72: 294-297. https://doi.org/10.1016/j.molcatb.2011.07.004
  5. Liu L, Zhang C, Guo WB, Xu L. 2016. Improved synthesis of eslicarbazepine acetate. Chin. J. Med. Chem. 26: 31-36.
  6. Ravinder B, Reddy SR, Sridhar M, Mohan MM, Srinivas K, Reddy AP. 2013. An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbazepine. Tetrahedron Lett. 54: 2841-2844. https://doi.org/10.1016/j.tetlet.2013.03.089
  7. Desai SJ, Pandya AK, Sawant SP, Mehariya KR. Process for preparation of enantiomers of licarbazepine. WIPO Patent Application WO/2011/117885.
  8. Li HY, Li ZY, Ruan GH, Yu YK, Liu XM. 2016. Asymmetric reduction of acetophenone into R-(+)-1-phenylethanol by endophytic fungus Neofusicoccum parvum BYEF07 isolated from Illicium verum. Biochem. Biophs. Res. Commun. 473: 874-878. https://doi.org/10.1016/j.bbrc.2016.03.142
  9. Birolli WG, Ferreira IM, Alvarenga N, Santos DA, Matos IL, Comasseto JV, et al. 2015. Biocatalysis and biotransformation in Brazil: an overview. Biotechnol. Adv. 33: 481-510. https://doi.org/10.1016/j.biotechadv.2015.02.001
  10. Singh M, Singh S, Deshaboina S, Krishnen H, Lloyd R, Holt-Tiffin K, et al. 2012. Asymmetric reduction of a key intermediate of eslicarbazepine acetate using whole cell biotransformation in a biphasic medium. Catal. Sci. Tech. 2: 1602-1605. https://doi.org/10.1039/c2cy00537a
  11. Shen L, Cheng KCK, Schroeder MK, Yang P, Marsh ENG, Lahann J, et al. 2016. Immobilization of enzyme on a polymer surface. Surf. Sci. 648: 53-59. https://doi.org/10.1016/j.susc.2015.10.046
  12. Wang LF, Zhu GY, Wang P, Zhang NB. 2005. Self-assembling of polymer-enzyme conjugates at oil/water interfaces. Biotechnol. Prog. 21: 1321-1328.
  13. Fainerman VB, Miller R. 2005. Equilibrium and dynamic characteristics of protein adsorption layers at gas-liquid interfaces: theoretical and experimental data. Colloid J. 67: 393-404. https://doi.org/10.1007/s10595-005-0110-8
  14. Zhu GY, Wang P. 2004. Polymer-enzyme conjugates can self-assemble at oil/water interfaces and effect interfacial biotransformations. J. Am. Chem. Soc. 126: 11132-11133. https://doi.org/10.1021/ja046853z
  15. Barbosa CG, Caseli L, Peres LO. 2016. Conjugated polymers nanostructured as smart interfaces for controlling the catalytic properties of enzymes. J. Colloid Interface Sci. 76: 206-213.
  16. Liu H, Zhang J, Luo X, Kong N, Cui L, Liu J. 2013. Preparation of biodegradable and thermoresponsive enzyme-polymer conjugates with controllable bioactivity via RAFT polymerization. Eur. Polym. J. 49: 2949-2960. https://doi.org/10.1016/j.eurpolymj.2013.04.013
  17. Bradford MM. 1976. Rapid and sensitive method for the quantitation of microgram quantities of protein: the principle of protein-dye binding. Anal. Biochem. 72: 248-255. https://doi.org/10.1016/0003-2697(76)90527-3
  18. Choi JM, Han SS, Kim HS. 2015. Industrial applications of enzyme biocatalysis: current status and future aspects. Biotechnol. Adv. 33: 1443-1454. https://doi.org/10.1016/j.biotechadv.2015.02.014
  19. Rodriguez C, Lavandera I, Gotor V. 2012. Recent advances in cofactor regeneration systems applied to biocatalyzed oxidative processes. Curr. Org. Chem. 16: 2525-2541. https://doi.org/10.2174/138527212804004643
  20. Muthineni N, Arnipally MS, Bojja S, Meshram HM, Adari BR. 2016. A green approach towards the synthesis of chiral alcohols using functionalized alginate immobilized Saccharomyces cerevisiae cells. J. Mol. Catal. B Enzym. 134: 233-237. https://doi.org/10.1016/j.molcatb.2016.10.016
  21. Liu ZQ, Dong SC, Yin HH, Xue YP, Tang XL, Zhang XJ, et al. 2017. Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system. Bioresour. Technol. 229: 26-32. https://doi.org/10.1016/j.biortech.2016.12.098
  22. Philips RS. 1996. Temperature modulation of the stereochemistry of enzymatic catalysis: prospects for exploitation. Trends Biotechnol. 14: 13-16. https://doi.org/10.1016/0167-7799(96)80908-5
  23. Xie Q, Wu JP, Lin L, Xu G, Yang LR. 2009. Purification and characterization of a carbonyl reductase from Candida pseudotropicalis. J. Chem. Eng. Chin. Univ. 23: 92-98.