Epoxide Hydrolases in Biocatalytic Applications

Epoxide hydrolases (EHs) are a versatile class of enzymes that catalyse the addition of water to epoxide rings, yielding vicinal diols with high regio- and enantioselectivity. They belong predominantly to the α/β-hydrolase fold superfamily and can be broadly classified into microbial, plant and mammalian isoforms, each displaying distinct substrate specificities and catalytic efficiencies. The two-step catalytic mechanism involves a conserved catalytic triad and a transient covalent intermediate, enabling EHs to process a wide range of aliphatic and aromatic epoxides. Their ability to resolve racemic mixtures or convert meso-epoxides into single enantiomer diols has positioned them as key biocatalysts for the synthesis of chiral building blocks in pharmaceutical and fine-chemical industries.

Recent advances in genome mining, metagenomic screening and high-throughput assays have expanded the portfolio of EHs available for biocatalysis. Protein engineering strategies—including directed evolution, semi-rational design and active-site mutagenesis—have enhanced catalytic activity, thermostability and enantioselectivity. Immobilisation on a variety of supports has further improved operational stability, recyclability and process intensification. Integration of EHs in multi-enzymatic cascades and in combination with green solvents has opened new avenues for sustainable chemical production and environmental remediation, from enantiopure diols to detoxification of epoxide pollutants.

Research from Nature Portfolio

Site-directed and loop engineering of a Phaseolus vulgaris epoxide hydrolase yielded variants with 1.7-fold higher specific activity and a threefold improvement in catalytic efficiency for aryl glycidyl ether kinetic resolution. Whole-cell biotransformations at gram scale produced (R)-epoxides with >99% enantiomeric excess under mild conditions. Separately, a bifunctional epoxide hydrolase/haloalkane dehalogenase from a marine yeast was shown to be highly inducible under xenobiotic stress, catalysing a broad range of epoxide and bromoalkane substrates. This dual activity highlights its potential for integrated bioremediation and biosensing of mixed pollutants, with expression tightly regulated by substrate availability.

Epoxide Hydrolases in Biocatalytic Applications publication trend

The graph below shows the total number of articles in epoxide hydrolases in biocatalytic applications across all publications each year (not limited to Nature Index journals).

Technical terms

Epoxide hydrolase (EH): Enzyme catalysing the hydrolysis of an epoxide ring to form a vicinal diol.

Enantioselectivity: Degree to which a catalyst favours formation of one enantiomer over its mirror image.

Directed evolution: Laboratory procedure involving iterative rounds of mutagenesis and selection to improve enzyme properties.

α/β-hydrolase fold: Common protein architecture comprising alternating α-helices and β-strands around a central β-sheet.

Immobilisation: Attachment of enzymes to solid carriers to enhance stability and facilitate reuse.

Catalytic triad: Three amino acid residues in an enzyme active site that cooperate to perform catalysis, typically Asp/His/Glu or Ser/Asp/His.

Epiconvergent reaction: Process in which both enantiomers of a racemic substrate are converted to a single product enantiomer.

References

1. Epoxide Hydrolases: Multipotential Biocatalysts. International Journal of Molecular Sciences (2023).
2. Improving Hydrolytic Activity and Enantioselectivity of Epoxide Hydrolase from Phanerochaete chrysosporium by Directed Evolution. Molecules (2024).
3. Deciphering the stereo-specific catalytic mechanisms of cis-epoxysuccinate hydrolases producing L(+)-tartaric acid. Journal of Biological Chemistry (2024).
4. Significant improvement in catalytic activity and enantioselectivity of a Phaseolus vulgaris epoxide hydrolase, PvEH3, towards ortho-cresyl glycidyl ether based on the semi-rational design. Scientific Reports (2020).
5. Ylehd, an epoxide hydrolase with promiscuous haloalkane dehalogenase activity from tropical marine yeast Yarrowia lipolytica is induced upon xenobiotic stress. Scientific Reports (2017).