Enzymatic synthesis of cephalosporins. The immobilized acylase from Arthrobacter viscosus: a new useful biocatalyst.
The acylase from Arthrobacter viscosus was immobilized, studied in the enzymatic synthesis of some cephalosporins by kinetically controlled N-acylation (kcNa) of different cephem nuclei, and compared with the penicillin G acylase (PGA) from Escherichia coli. The reaction outcomes were dependent on the acylase microbial source and on the type of immobilization support. Generally, both enzymes, when immobilized onto hydrophilic resins such as glyoxyl-agarose (activated with aldehyde groups), displayed higher synthetic performances in comparison with hydrophobic acrylic epoxy-supports like Eupergit C. The kcNa of 7-amino cephalosporanic acid catalyzed by A. viscosus immobilized on glyoxyl-agarose afforded a quantitative conversion in 7-[(1-hydroxy-1-phenyl)-acetamido]-3-acetoxymethyl-Delta(3)-cephem-4-carboxylic acid, a useful intermediate for the synthesis of Cefamandole and Cefonicid. Similar results were obtained in the synthesis of these cephalosporins by direct acylation of the corresponding 3'-functionalized nucleus. In these reactions, A. viscosus displayed higher synthetic performances than the PGA from E. coli.
Terreni
Marco
M
Italian Biocatalysis Center, PBL Dipartimento di Chimica Farmaceutica, via Taramelli 12, Università degli Studi, I-27100, Pavia, Italy. markt@ibiocat.eu
Ubiali
Daniela
D
Bavaro
Teodora
T
Pregnolato
Massimo
M
Fernández-Lafuente
Roberto
R
Guisán
José M
JM
D000581:Amidohydrolases / Q000378:metabolism*; D001173:Arthrobacter / Q000201:enzymology* / Q000378:metabolism; D002384:Catalysis; D002511:Cephalosporins / Q000096:biosynthesis* / Q000737:chemistry; D004800:Enzymes, Immobilized / Q000378:metabolism*
D002511:Cephalosporins; D004800:Enzymes, Immobilized; D000581:Amidohydrolases; C019665:amidase