Lyase example

In biochemical parlance, these systems are called mutases, or sometimes isomerases. When Z = OH and Y = OH or NHj, the product eliminates an aldehyde and either HjO or NH3 so that the process is irreversible. Such systems sometimes are referred to as eliminases, dehydrases or ammonia-lyases. Examples of these various types of systems are shown by the first five examples in Figure 8.3, where (CoA)—S represents coenzyme A. It should be noted that the amino mutases, such as ornithine amino mutase, also require pyridoxal phosphate as a cofactor. 

Attention has been drawn to the potential of phosphoric acid anhydrides of nucleoside 5 -carboxylic acids (14) as specific reagents for investigating the binding sites of enzymes. For example, (14 B = adenosine) inactivates adenylosuccinate lyase from E. coli almost completely, but has little effect on rabbit muscle AMP deaminase. The rate of hydrolysis of (14) is considerably faster than that of acetyl phosphate, suggesting intramolecular assistance by the 3 -hydroxyl group or the 3-nitrogen atom. 

Griengl reported the first example of hydroxynitrile lyase-catalyzed cyanohydrin formation in a mixed solvent system of [bmim][BF4] and buffer (pH 3.7) (1 1) (Fig. 19). In the reaction, a mixed solvent system was essential, but excellent results were obtained. 

C-P lyase has a broad snbstrate specificity and, for example, dimethyl phosphonate is degraded to methane, methylphenyl phosphonate to benzene, and the degradation of the widely nsed herbicide glyphosate may follow alternative pathways both of which involve C-P fission. 

These protruding structures may form catalytic sites or binding sites for small molecules. Remarkably, some polysaccharide modification enzymes of pathogenic bacteria are similar to enzymes of their host cells. For example, during cell development, pectin, a principal component in the primary cell wall of plants, is modified by its own pectin methylesterases that have /1-solenoid structures (Johansson et al, 2002) and in this respect, resemble pectin lyases secreted by bacteria to break down these structures (Lietzke et al., 1996). 

Based on the same principle, there are monomeric / -helical proteins that carry at their extremities a cluster of helical or nonrepetitive structures that could act as a capping element covering their exposed ends (Emsley et al., 1996 Lietzke et al, 1994 Petersen et al, 1997 Steinbacher et al, 1994). For example, the last 40 residues of pectate lyase C form a large loop that partially covers the surface of the /Hielix (Yoder et al, 1993). The fibrous (or otherwise elongated) domain of these natural /f-stranded proteins is not stable in isolation, as for example in the case of the P22 tailspike where bacterially expressed isolated /Hielix domain, at high concentrations, forms fibrous aggregates that bind Congo red (Schuler et al, 1999). 

Carbon-carbon bond lyases, used in the reverse, synthetic direction have also enjoyed significant application in the pharmaceutical industry. For example 7/-acetyl-D-neuraminic acid (NANA), an intermediate in the chemoenzymatic synthesis of the influenza virus sialidase inhibitor zanamavir, may be synthesized using NANA aldolase. 

Miiller and co-workers have developed an enantioselective enzymatic crossbenzoin reaction (Table 2) [43, 44], This is the first example of an enantioselective cross-benzoin reaction and takes advantage of the donor-acceptor concept. This transformation is catalyzed by thiamin diphosphate (ThDP) 23 in the presence of benzaldehyde lyase (BAL) or benzoylformate decarboxylase (BFD). Under these enzymatic reaction conditions the donor aldehyde 24 is the one that forms the acyl anion equivalent and subsequently attacks the acceptor aldehyde 25 to provide a variety of a-hydroxyketones 26 in good yield and excellent enantiomeric excesses without contamination of the other cross-benzoin products 27. The authors chose 2-chlorobenzaldehyde 25 as the acceptor because of its inability to form a homodimer under enzymatic reaction conditions. 

PLP-dependent enzymes catalyze the following types of reactions (1) loss of the ce-hydrogen as a proton, resulting in racemization (example alanine racemase), cyclization (example aminocyclopropane carboxylate synthase), or j8-elimation/replacement (example serine dehydratase) (2) loss of the a-carboxylate as carbon dioxide (example glutamate decarboxylase) (3) removal/replacement of a group by aldol cleavage (example threonine aldolase and (4) action via ketimine intermediates (example selenocysteine lyase). 

This chapter covers some general aspects of the use of enzymes in aqueous and organic media. Although lipases are the most common biocatalysts in these processes [4], other hydrolytic enzymes such as esterases and nitrilases have also shown their utility in the manufacture of pharmaceuticals. In addition, some representative examples using oxidoreductases and lyases will be also discussed. 

The use of this kind of lyases has been exploited in organic synthesis by several groups using (R)-and (S)-oxynitrilases for the synthesis of a great variety of organic compounds. A representative example of the utility of this reaction in the synthesis of pharmaceuticals is the preparation of adrenergic bronchodilators [51]. Scheme 10.22 shows a chemoenzymatic route to (R)-terbutaline. 

In the past decade, a few examples of benzoannulated carbazole ring systems were found in nature as marine products. In 1993, Chan et al. reported a novel marine benzocarbazole alkaloid, purpurone (281) from the marine sponge lotrochota sp. in its racemic form. Purpurone, as indicated by its name, is purple in color. This represents the first example of a benzocarbazole alkaloid with a biphenylene quinone methide functionality. The isolate showed ATP-citrate lyase (ACL) inhibitory activity (247). 

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