Microbial epoxide hydrolases

Active hits were found for every type of substrate screened, including those for which other known microbial epoxide hydrolases were ineffective. For example, hydrolysis of m-stilbenc oxide was not successful with several microbial EHs tested previously.4243 By contrast, several of our new enzymes actively hydrolyzed this substrate and exhibited excellent enantioselectivities (>99% ee). It is important to note that these enzymes were found to be capable of selectively hydrolyzing a wide range of mc.vo-cpoxidcs, including cyclic and acyclic alkyl- and aryl-substituted substrates. 

Similar results were described by Mamouhdian and Michael, who isolated 18 bacterial strains able to produce optically enriched epoxides with excellent ee s (up to 98%) [104, 105]. However, in the case of trflns-(2J ,3J )-epoxybutane, it was shown that the enantiomeric enrichment is in fact due to a second-step enantioselective hydrolysis of the epoxide, which is first produced in racemic form. This, interestingly, is an unexpected example of the possible use of microbial epoxide hydrolases for the synthesis of enantiopure epoxides (see below). 

The compatibility of microbial epoxide hydrolases with organic solvents deserves a special comment. It has been reported that in the majority of cases, the addition of water-miscible or -immiscible organic (co) solvents has negative effects on the activity. This is particularly true for bacterial enzymes, which showed total deactivation 124l On the other hand, several epoxide hydrolases from yeasts and fungi seem... 

Steinreiber A, Faber K. Microbial epoxide hydrolases for preparative biotransformations. Current Opinion in Biotechnology 12(6), 552, 2001. 

As a result, an impressive amount of knowledge on microbial epoxide hydrolases from various sources - such as bacteria, filamentous fungi, and yeasts - has been gathered and featured in several reviews [594-598]. The data available to date indicate that the enantioselectivities of enzymes from certain microbial sources can be correlated to the substitutional pattern of various types of substrates [599] ... 

Scheme 2.93 Enzymatic resolution of 2,2-disubstituted epoxides using microbial epoxide hydrolases...

Recent developments in the asymmetric hydrolytic ring opening of epoxides catalysed by microbial epoxide hydrolase. Tetrahedron Asymmetry, 21 (24), 2879-2898. 

Hwang, S., Choi, C.Y. and Lee, E.Y. (2008) One-p>ot biotransformation of racemic styrene oxide into (R)-l,2-phenylethanediol by two recombinant microbial epoxide hydrolases. Biotechnol. Bioprocess Eng., 13,453-457. 

Kotik, M., Brichac, J. and Kyslik, P (2005) Novel microbial epoxide hydrolases for biohydrolysis of glycidyl derivatives. /. BiotechnoL, 120, 364—375. 

Stereoselective Syntheses Using Microbial Epoxide Hydrolases... 

The search for novel microbial epoxide hydrolases through title screening of various fungal and bacterial sources was mainly triggered by chance observations of unexpected side reactions in microbial transformations within two research groups at about the same time. 

An application of microbial epoxide hydrolases for the synthesis of a-bisabolol, one of the stereoisomers (out of four) of interest for the cosmetic industry, is illustrated in Scheme 17. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane diastereoisomers obtained by chemical synthesis from (/ )- or (5-limonene [130]. Thus, starting from (S)-limonene, the biohydrolysis of the mixture of (4S,8i S) epoxides... 

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