Lipases epoxide hydrolases

The use of enzymes and whole cells as catalysts in organic chemistry is described. Emphasis is put on the chemical reactions and the importance of providing enantiopure synthons. In particular kinetics of resolution is in focus. Among the topics covered are enzyme classification, structure and mechanism of action of enzymes. Examples are given on the use of hydrolytic enzymes such as esterases, proteases, lipases, epoxide hydrolases, acylases and amidases both in aqueous and low-water media. Reductions and oxidations are treated both using whole cells and pure enzymes. Moreover, use of enzymes in sngar chemistiy and to prodnce amino acids and peptides are discnssed. 

In biocatalysis, hydrolases are the most important class of enzymes for carrying out enzymatic resolutions. Many hydrolases, such as esterases, lipases, epoxide hydrolases, proteases, peptidases, acylases, and amidases, are commercially available a substantial number of them are bulk enzymes [87]. Resting-cell systems, if they are not immobilized, are used in diluted suspensions and could be handled as quasi-homogeneous catalysts. 

Although the hydrolysis of esters with lipases and esterases represents the most common process to obtain chiral intermediates for the synthesis of pharmaceuticals, proteases and other hydrolytic enzymes such as epoxide hydrolases and nitrilases have also been used for this purpose. We show here a few representative examples of the action of these biocatalysts that have been recently published. 

Epoxide hydrolases are less used than lipases however, in recent years the synthesis of chiral diols with these biocatalysts has emerged as an excellent methodology to develop new and interesting chemoenzymatic processes [13],... 

Wong, C.-H., Whitesides, G. M. Chapter 2 Use of Hydrolytic Enzymes Amidases, Proteases, Esterases, Lipases, Nitrilases, Phosphatases, Epoxide Hydrolases. In Enzymes in Synthetic Organic Chemistry, Elsevier New York, 1994, p. 41. 

Clan SC peptidases are a/p hydrolase-fold enzymes that consist of parallel P-strands surrounded by a-helices. The a/p hydrolase-fold provides a versatile catalytic platform that, in addition to achieving proteolytic activity, can either act as an esterase, lipase, dehalogenase, haloperoxidase, lyase, or epoxide hydrolase (18). Six phylogenetically distinct families of clan SC are known, and oifly four of them have known structure. Catalytic amenability of the a/p hydrolase-fold may underlie why clan SC peptidases are the second largest family of serine peptidases in the human genome. Other mechanistic classes need not use the catalytic serine and instead use cysteine or glutamic acid (19). Clan SC peptidases present an identical geometry to the catalytic triad observed in clans PA and SB, yet this constellation is ordered differently in the polypeptide sequence. Substrate selectivity develops from the a-helices that surround the central P-sheet core. Within clan SC, carboxypeptidases from family SIO are unique for their ability to maintain... 

Keywords Enantiopure epoxides. Oxidative enzymes. Cytochrome P-450, co-hydroxylases. Methane monooxygenases. Lipases, Microbial oxidations. Epoxide hydrolases. Biotransformations. 

As a conclusion, examination of the present literature clearly indicates that, depending on the circumstances, any of the methods described in this review may be the best for the preparation of a given enantiopure epoxide. In particular, the recent progress achieved by using metal-catalyzed chemical processes obviously has to be taken into account. As far as biocatalytic methods are concerned, one can anticipate that, in the near future, lipases or, better, epoxide hydrolases, will prove to be the best choice, particularly as far as industrial applications are concerned. Research is ongoing in diverse laboratories to explore the scope and limitations of these very promising enzymes. 

Hydrolases None Lipases Esterases Galactosidases, glucosidases Epoxide hydrolases Peptidases, peptidohydrolase Acylases Amidases, amidohydrolases Nitrilases Hydantoinases... 

In industrial biotransformations, hydrolytic reactions occupy a prominent position for the production of optically active amines, alcohols, and carboxylic acids. Compared with other reactions, hydrolytic reactions are feasible to scale up because they are cofactor-free, relatively simple, and chemically tunable systems. In addition to home-made whole-cell biocatalysts, which are considered to be more cost-effective for specific syntheses, some commercially available hydrolases, including lipases/esterases, epoxide hydrolases, nitrilases, and glycosidases, are also employed for the enantioselective production of chiral chemicals. 

Successful examples were demonstrated for transesterilication, perhydrolysis and ammonolysis (using lipases, esterases, and proteases), amide/peptide synthesis (using proteases), epoxide hydrolysis (using epoxide hydrolases), and glycoside synthesis (using glycosidases). Even redox-transformations, such as carbonyl reduction and sulfoxidation were possible [113-119]. 

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