Acylase biocatalysis

Scheme 20.17 Approach to arylalanines that combines asymmetric hydrogenation and acylase biocatalysis.

In summary, the formation of optically active compounds through hydrolysis reactions is dominated by biocatalysis mainly due to the availability and ease of use of a wide variety of esterases, lipases and (to a lesser extent) acylases. Epoxide ring-opening (and related reactions) is likely to be dominated by salen-metal catalysts while enzyme-catalysed nitrile hydrolysis seems destined to remain under-exploited until nitrilases or nitrile hydratases become commercially available. 

The use of biocatalysis for the production of chemicals started to receive serious interest in the 1960s with the development of immobilized aminoacylases for the production of chirally pure amino acids by Tanabe Seigaku of Japan, as well as the application of penicillin acylase for the production of 6-aminopenicillanic acid (6-APA), a key... 

One of the inherent advantages of enzymes is the ability to discriminate between stereoisomers, often generating products with ena-tiomeric excesses (i.e., of over 98%). Judicious application of biocatalysis can also reduce the number of chemical steps needed to synthesize certain drugs, leading to hybrid chemoenzymatic processes with lower costs and less waste. The range of enzymes used in the synthesis of chiral intermediates has expanded beyond esterases and acylases and... 

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. 

ADCA (cephalosporins) Fermentation and biocatalysis metabolic engineering, acylase... 

The resolution of N-acetyl-D,L-amino acids to prepare non-natural l- and D-amino acids was the beginning of applied biocatalysis, and aminobutyric and di-amino-butyric acids as well as beta-D,L-phenylalanines can be resolved. A series of microbial acylases from Streptomyces, Alcaligenes, Comamonas and Pseudomonas species were produced for these applications. Immobilized acylase on Eupergit C or the use of membrane reactors allow the facile production of such chiral amino acids. 

Bruggink A (2000), Green solutions for chemical challenges biocatalysis in the synthesis of semi-synthetic antibiotics. In Zwanenburg B, Mikolajczyk M, Kielbasinsky P (eds) Enzymes in action. NATO sciences series 1/33, Kluwer Academic, pp 449-458 Bruggink A, Roos EC, de Vroom E (1998) Penicillin acylase in the industrial production of lactam antibiotics.Org Process Res Dev2 128-133... 

Finally, several other animal tissues yield useful enzymes that have been employed in S5mthesis. Pepsin is an important digestive protease from animal stomach whose native role is hydrolyzing amide bonds involving hydrophobic, aromatic amino adds, for example, phenylalanine, tyrosine, and tryptophan. Acylase from pordne kidney sdectivdy hydrolyzes N-acetyl amino adds and is commercially available. It has long been used for kinetic resolutions of amino adds. In addition to hydrolases, other animal enzymes have found important applications in biocatalysis. Rabbit musde aldolase is commerdally awiilable and was shown to catalyze aldol condensations between dihydroxyacetone phosphate and various nonnatural aldehydes by the Whitesides group in 1989 [10]. This seminal report touched off an avalanche of new applications for this and related enzymes in asymmetric synthesis. 

Traditional techniques such as physical adsorption and covalent linkage onto solid supports, entrapment in polymer matrices, and microencapsulation have long been used for immobilizing such enzymes as lipases, proteases, hydantoinases, acylases, amidases, oxidases, isomerases, lyases, and transferases [12-18]. Encapsulation and adsorption have also proved their utility in the immobilization of bacterial, fungal, animal, and plant cells [12-21]. However, as biocatalysis applications have grown, so the drawbacks and limitations of traditional approaches have become increasingly evident. The forefront issues now facing bioimmobilization are indicated in Table 1. 

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