Enzymatic transformations. Part 58: Enantioconvergent biohydrolysis of styrene oxide derivatives catalysed by the Solanum tuberosum epoxide hydrolase

Enantioconvergent production of (R)‐1‐phenyl‐1,2‐ethanediol from styrene oxide by combining the Solanum tuberosum and an evolved Agrobacterium radiobacter AD1 epoxide hydrolases

“…Interest in using epoxide hydrolases (EHs, EC 3.3.2.3), enzymes that hydrolyze epoxides to diols for synthesis of enantio-pure compounds (Manoj et al, 2001), is increasing for the production of pharmaceuticals (Monterde et al, 2004;Schoemaker et al, 2003). For example, the pharmaceutical intermediate, enantio-pure (R)-or (S)-mandelic acid, is used in the synthesis of b-lactam antibiotics and analytical reagents (Groger, 2001), and (R)-mandelic acid may be made from (R)-1-phenyl-1,2-ethanediol (Drummond et al, 1990;Lindstad et al, 1998).…”

“…The hydrolysis of racemic styrene oxide with StEH has been investigated and demonstrated to be an enantioconvergent process with initial attack on the a (benzylic) carbon atom of (S)-styrene oxide to form (R)-1-phenyl-1,2-ethanediol followed by hydrolysis of the b (terminal carbon) atom of (R)-styrene oxide to form again (R)-1-phenyl-1,2-ethanediol ( Fig. 1B) (Monterde et al, 2004). Therefore, this single enzyme was used to form (R)-1-phenyl-1,2-ethanediol from racemic styrene oxide at 86% enantiomeric excess at 100% conversion (Monterde et al, 2004) although the rate is 300-fold slower for the (R)-styrene oxide reaction.…”

Protein engineering for development of new hydrolytic biocatalysts

“…A similar study on an epoxide hydrolase from Aspergillus niger M200 resulted in a mutant that after having accumulated nine residue replacements afforded the formation of the (S)-enantiomers of the hydrolysis products of styrene oxide to an enantiomeric excess of 70% [37]. The ability of epoxide hydrolases to produce enantiomerically pure products from racemic starting epoxides by enantioconvergence was reported already ten years ago by the Furstoss group who analyzed the product outcome from StEH1 catalyzed hydrolysis of styrene oxide derivatives [38]. In a recent report, a similar behavior has been observed in another plant-derived isoenzyme from Vigna radiata that produces the (R)-diol product with an enantiomeric product excess of 70% from a racemic mixture of 4-nitrostyrene oxide [39].…”

Fluorescence Assays for Biotransformations

“…Indeed epoxide hydrolases enzymes may catalyze epoxide opening at both sides of the epoxide, leading to enantiomeric products [44] . Alternatively, the enzyme reaction may also lead to an enantioconvergent hydrolysis where a racemic epoxide is converted to a single enantiomer of the 1,2 -diol [45] .…”