Catalysis Letters

, Volume 149, Issue 2, pp 629–637 | Cite as

Exploring the Biocatalytic Scope of a Novel Enantioselective Halohydrin Dehalogenase from an Alphaproteobacterium

  • Feng XueEmail author
  • Xiangju Ya
  • Yuansong Xiu
  • Qi Tong
  • Yuqi Wang
  • Xinhai Zhu
  • He HuangEmail author


A gene encoding halohydrin dehalogenase from an alphaproteobacterium (AbHHDH) was identified, cloned and over-expressed in Escherichia coli. AbHHDH was able to catalyze the stereoselective dehalogenation of prochiral and racemic halohydrins. It showed the highest enantioselectivity in the dehalogenation of 20 mM (R,S)-2-bromo-1-phenylethanol, which yielded (S)-2-bromo-1-phenylethanol with 99% ee and 34.5% yield. Moreover, AbHHDH catalyzed the azidolysis of epoxides with low to moderate (S)-enantioselectivity. The highest enantioselectivity (E = 18.6) was observed when (R,S)-benzyl glycidyl ether was used as the substrate. A sequential kinetic resolution catalyzed by HHDH was employed for the synthesis of chiral 1-chloro-3-phenoxy-2-propanol. We prepared enantiopure (S)-isomer with a high enantiopurity of ee > 99% and a yield of 30.7% (E-value: 21.3) by kinetic resolution of 20 mM substrate. The (S)-isomer with 99% ee readily obtained from 40 to 150 mM (R,S)-1-chloro-3-phenoxy-2-propanol. Taken together, the results of this study demonstrate the applicability of this HHDH for the production of optically active compounds.


Halohydrin dehalogenase Epoxides Halohydrins Enantioselectivity Biocatalysis 



This project was sponsored by the National Natural Science Foundation of China (No. 21606192), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 16KJB180029) and the China Postdoctoral Science Foundation (No. 2016M601795).

Compliance with Ethical Standards

Conflict of interest

The authors declared that they have no conflicts of interest to this work.

Supplementary material

10562_2019_2659_MOESM1_ESM.docx (426 kb)
Supplementary material 1 (DOCX 426 KB)


  1. 1.
    Schallmey A, Schallmey M (2016) Appl Microbiol Biotechnol 100:7827CrossRefGoogle Scholar
  2. 2.
    You ZY, Liu ZQ, Zheng YG (2013) Appl Microbiol Biotechnol 97:9CrossRefGoogle Scholar
  3. 3.
    Dijoux GH, Elenkov MM, Spelberg JHL et al (2008) ChemBioChem 9:1048CrossRefGoogle Scholar
  4. 4.
    Kasai N, Tsujimura K, Unoura K et al (1992) J Ind Microbiol Biotechnol 10:37Google Scholar
  5. 5.
    Kasai N, Tsujimura K, Unoura K et al (1992) J Ind Microbiol Biotechnol 9:97Google Scholar
  6. 6.
    Kasai N, Suzuki T, Furukawa Y (1998) Chirality 10:682CrossRefGoogle Scholar
  7. 7.
    Nakamura T, Nagasawa T, Yu F et al (1992) J Bacteriol 174:7613CrossRefGoogle Scholar
  8. 8.
    Spelberg JHL, Vlieg JETV, Bosma T et al (1999) Tetrahedron 10:2863CrossRefGoogle Scholar
  9. 9.
    Hasnaoui G, Spelberg JHL, Vries ED et al (2005) Tetrahedron 16:1685CrossRefGoogle Scholar
  10. 10.
    Mikeušević A, Primožič I, Hrenar T et al (2016) Tetrahedron 27:930CrossRefGoogle Scholar
  11. 11.
    Elenkov MM, Hauer B, Janssen DB (2006) Adv Synth Catal 348:579CrossRefGoogle Scholar
  12. 12.
    Elenkov MM, Primozic I, Hrenar T et al (2012) Org Biomol Chem 10:5063CrossRefGoogle Scholar
  13. 13.
    Koopmeiners J, Diederich C, Solarczek J et al (2017) ACS Catal 7:6877CrossRefGoogle Scholar
  14. 14.
    Chen SY, Yang CX, Wu JP et al (2013) Adv Synth Catal 355:3179CrossRefGoogle Scholar
  15. 15.
    Ma SK, Gruber J, Davis C et al (2010) Green Chem 12:81CrossRefGoogle Scholar
  16. 16.
    Fox RJ, Davis SC, Mundorff EC et al (2007) Nat Biotechnol 25:338CrossRefGoogle Scholar
  17. 17.
    SchallmeyM KoopmeinersJ, Wells E et al (2014) Appl Environ Microbiol 80:7303CrossRefGoogle Scholar
  18. 18.
    Koopmeiners J, Halmschlag B, Schallmey M et al (2016) Appl Microbiol Biotechnol 100:7517CrossRefGoogle Scholar
  19. 19.
    Wan NW, Liu ZQ, Huang K et al (2014) RSC Adv 4:64027CrossRefGoogle Scholar
  20. 20.
    Xue F, Liu ZQ, Wan NW et al (2014) Appl Biochem Biotechnol 174:352CrossRefGoogle Scholar
  21. 21.
    Xue F, Liu ZQ, Wang YJ et al (2015) J Mol Catal B-Enzym 115:105CrossRefGoogle Scholar
  22. 22.
    Xue F, Gao J, Zhang L et al (2018) Catal Lett 148:1181CrossRefGoogle Scholar
  23. 23.
    Shapenvoa DS, Belyatskii MK, Panicheva LP (2010) Russ J Org Chem 46:1017CrossRefGoogle Scholar
  24. 24.
    Liu ZQ, Wu L, Zhang XJ et al (2017) J Agr Food Chem 65:3721CrossRefGoogle Scholar
  25. 25.
    Zhao J, Chu YY, Li AT et al (2011) Adv Synth Catal 353:1510CrossRefGoogle Scholar
  26. 26.
    Wu K, Wang HL, Sun HH et al (2015) Appl Microbiol Biotechnol 99:9511CrossRefGoogle Scholar
  27. 27.
    Wu SK, Li AT, Chin YS et al (2013) ACS Catal 3:752CrossRefGoogle Scholar
  28. 28.
    Ulrich A, Volker M, Manfred PS (1993) Chirality 5:554CrossRefGoogle Scholar
  29. 29.
    Xu Y, Xu JH, Pan J et al (2004) J Mol Catal B 27:155CrossRefGoogle Scholar
  30. 30.
    Chen CS, Fujimoto Y, Girdaukas G et al (1982) J Am Chem Soc 104:7294CrossRefGoogle Scholar
  31. 31.
    de Jong RM, Rozeboom HJ, Kalk KH et al (2002) Acta Crystallogr D 58:176CrossRefGoogle Scholar
  32. 32.
    Nagasawa T, Nakamura T, Yu F et al (1992) Appl Microbiol Biotechnol 36:478CrossRefGoogle Scholar
  33. 33.
    Assis HMS, Bull AT, Hardman DJ (1998) Enzyme Microb Technol 22:545CrossRefGoogle Scholar
  34. 34.
    Nakamura T, Nagasawa T, Yu FJ et al (1994) Appl Environ Microbiol 60:1297Google Scholar
  35. 35.
    Liu ZQ, Gao AC, Wang YJ et al (2014) J Ind Microbiol Biotechnol 41:1145CrossRefGoogle Scholar
  36. 36.
    Xue F, Liu ZQ, Wang YJ et al (2015) Catal Commun 72:147CrossRefGoogle Scholar
  37. 37.
    Guo C, Chen Y, Zheng Y et al (2015) Appl Environ Microbiol 81:2919CrossRefGoogle Scholar
  38. 38.
    Schrittwieser JH, Lavandera I, Seisser B et al (2009) Eur J Org Chem 14:2293CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Marine and BioengineeringYancheng Institute of TechnologyYanchengPeople’s Republic of China
  2. 2.College of Pharmaceutical ScienceNanjing Tech UniversityNanjingPeople’s Republic of China
  3. 3.School of Environmental and Chemical EngineeringJiangsu University of Science and TechnologyZhenjiangPeople’s Republic of China

Personalised recommendations