Structure-function relationships of epoxide hydrolases and their potential use in biocatalysis.
BACKGROUND
Chiral epoxides and diols are important synthons for manufacturing fine chemicals and pharmaceuticals. The epoxide hydrolases (EC 3.3.2.-) catalyze the hydrolytic ring opening of epoxides producing the corresponding vicinal diol. Several isoenzymes display catalytic properties that position them as promising biocatalytic tools for the generation of enantiopure epoxides and diols.


METHODS
This review focuses on the present data on enzyme structure and function in connection to biocatalytic applications. Available data on biocatalysis employed for purposes of stereospecific ring opening, to produce chiral vicinal diols, and kinetic resolution regimes, to achieve enantiopure epoxides, are discussed and related to results gained from structure-activity studies on the enzyme catalysts. More recent examples of the concept of directed evolution of enzyme function are also presented.


CONCLUSIONS
The present understanding of structure-activity relationships in epoxide hydrolases regarding chemical catalysis is strong. With the ongoing research, a more detailed view of the factors that influence substrate specificities and stereospecificities is expected to arise. The already present use of epoxide hydrolases in synthetic applications is expected to expand as new enzymes are being isolated and characterized. Refined methodologies for directed evolution of desired catalytic and physicochemical properties may further boost the development of novel and useful biocatalysts.


CONCLUSIONS
The catalytic power of enzymes provides new possibilities for efficient, specific and sustainable technologies to be developed for production of useful chemicals.
Widersten
Mikael
M
Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, SE-751 23 Uppsala, Sweden. mikael.widersten@biorg.uu.se
Gurell
Ann
A
Lindberg
Diana
D
D055162:Biocatalysis; D002384:Catalysis; D020134:Catalytic Domain; D004851:Epoxide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity
D004852:Epoxy Compounds; D021122:Protein Subunits; D010105:Oxygenases; C119721:limonene 1,2-monooxygenase; D004851:Epoxide Hydrolases