Recent advances on halohydrin dehalogenases—from enzyme identification to novel biocatalytic applications

Abstract

Halohydrin dehalogenases are industrially relevant enzymes that catalyze the reversible dehalogenation of vicinal haloalcohols with formation of the corresponding epoxides. In the reverse reaction, also other negatively charged nucleophiles such as azide, cyanide, or nitrite are accepted besides halides to open the epoxide ring. Thus, novel C-N, C-C, or C-O bonds can be formed by halohydrin dehalogenases, which makes them attractive biocatalysts for the production of various β-substituted alcohols. Despite the fact that only five individual halohydrin dehalogenase enzyme sequences have been known until recently enabling their heterologous production, a large number of different biocatalytic applications have been reported using these enzymes. The recent characterization of specific sequence motifs has facilitated the identification of novel halohydrin dehalogenase sequences available in public databases and has largely increased the number of recombinantly available enzymes. These will help to extend the biocatalytic repertoire of this enzyme family and to foster novel biotechnological applications and developments in the future. This review gives a general overview on the halohydrin dehalogenase enzyme family and their biochemical properties and further focuses on recent developments in halohydrin dehalogenase biocatalysis and protein engineering.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-016-7750-y) contains supplementary material, which is available to authorized users.

Haloperoxidases as catalysts in organic synthesis

“…Halohydrin dehalogenases (Hhe), for example, catalyse the reversible interconversion of epoxides into halohydrins (Scheme 1). 3 Also a range of halogenating monooxygenases (halogenases, MO) are known (Scheme 1). [4][5][6][7][8][9][10] Finally, halogenating peroxidases (haloperoxidases, HPO) are enzymes which oxidatively activate halides to the corresponding hypohalites at the expense of peroxides.…”

Selective Ring‐Opening of Di‐Substituted Epoxides Catalysed by Halohydrin Dehalogenases

“…Enzymes are attractive catalysts as they offer the possibility to attain building blocks through highly regio‐, stereo‐, and chemoselective transformations. In this sense, halohydrin dehalogenases (HHDHs, also called haloalcohol dehalogenases or halohydrin hydrogen‐halide‐lyases), initially discovered for their ability to degrade halogenated compounds, are very useful biocatalysts that catalyse the reversible dehalogenation of vicinal haloalcohols via formation of the corresponding epoxides ,. For a practical application of HHDHs, their promiscuous epoxide ring‐opening activity with a range of small anionic nucleophiles such as azide, cyanide, nitrite, cyanate or thiocyanate is even more attractive as it enables the regio‐ and stereoselective formation of novel C−N, C−C, C−O and C−S bonds ,.…”

Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor

“…The high cost of wastewater treatment has one of the primary drawbacks of this method, therefore, hindering the scale‐up production of ECH by the glycerol route. Alternatively, a greener approach with enzyme‐catalyzed dehalogenation was developed for producing ECH from 1,3‐DCP under mild conditions …”

“…Halohydrin dehalogenase (HHDH, EC 4.5.1.X) can catalyze the dehalogenation of vicinal halohydrins to produce their corresponding epoxides . HHDH‐mediated dehalogenation has several advantages over the other routes, such as eco‐friendly reaction conditions, a cheap starting material, and the lack of necessity for an externally added cofactor .…”