Penicillin G amidase PGA

We also wanted to evaluate the disassembly of our dendritic system under physiological conditions. Thus, we synthesized a self-immolative AB6 dendron 32 with water-soluble tryptophan tail units and a phenylacetamide head as a trigger (Fig. 5.26) to evaluate disassembly in aqueous conditions. The phenylacetamide is selectively cleaved by the bacterial enzyme penicillin G amidase (PGA). The trigger was designed to disassemble through azaquinone methide rearrangement and cyclic dimethylurea elimination to release a phenol intermediate that will undergo six quinone methide elimination reactions to release the tryptophan tail units. 

Penicillin G Amidase Origin E. coli overproducer Roche Diagnostics Penicillin G Amidase (PGA-450) Industrial... 

The optically active 3-amino ester (S)-51 has been nsed in the synthesis of xemilofiban. The resolution of ( )-52 was efficiently achieved by enzymatic acylation using immobilized penicillin G amidase (PGA-450) and phenylacetic acid as the acyl donor. The reaction was carried out at pH 5.7 and 28°C to yield the phenylacetamide (R)-53 and the unreacted 3-amino ester (S)-51 which were isolated in >99% ee and 98% ee, respectively. This bioconversion was used to resolve 6.1 kg of amine, from which the required (S)-51 was isolated in >96% ee and >43% yield [105]. 

Penicillin G acylase (PGA, EC 3.5.1.11, penicillin G amidase) catalyzes the hydrolysis of the phenylacetyl side chain of penicillin to give 6-aminopenicillanic acid. PGA accepts only phenylacetyl and structurally similar groups (phenoxyacetyl, 4-pyridylacetyl) in the acyl moiety of the substrates, whereas a wide range of structures are tolerated in the amine part [100]. A representative selection of amide substrates, which have been hydrolyzed in a highly selective fashion, is depicted in Figure 6.36. 

FIGURE 5.37 Chemical structure of a molecular probe with UV-Vis and fluorescence outputs for penicillin G amidase activity. The phenylacetamide group (red) is a substrate for PGA. The reporter units, 4-nitrophenol and 6-aminoquinoline, provide a visible signal and a fluorescence signal, respectively, upon release. (See the color version of this figure in Color Plates section.)... 

Lactams, i.e., penicillins and cephalosporins, represent the most important class of antibiotics. Penicillins consist of a common core, 6-aminopenicillanic acid (6-APA) and different side chains. Penicillin G (pen G), with a phenyl acetate side chain, and penicillin V (pen V), with a phenoxyacetate side chain, are fermented from the fungus Penicillium chrysogenum all the others are produced from 6-APA, which nowadays is produced mostly from pen G via penicillin G amidase (pen G amidase, pen G acylase, PGA, E.C. 3.5.1.11 Figure 7.33). Cephalosporins feature 7-aminocephalosporanic acid (7-ACA) or its deacetyl-form, 7-aminodesacetyl-cephalosporanic add (7-ADCA) as their common core cephalosporin C (Ceph C) is obtained through fermentation, and all the others are derived from 7-A(D)CA. 

Fig. 4. Operational stability of penicillin G amidase immobilized on epoxy carrier. Batch cycles were run in a 1.5-1 laboratory reactor at 10% penicillin G, 6 kU L 36 °C. pH was maintained at 8.0 by the addition of 2 N NH3. Initial splitting time was 65 min. The initial activity (relative base consumption per min at the beginning of each batch conversion) is plotted against the cycle number. PGA was immobilized on polymethacrylate with an epoxy density >2000 pmol g" (squares) or of 600 pmol g" (triangles)...

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