Enzymatic synthesis of beta-lactam antibiotics using penicillin-G acylase in frozen media.
Penicillin-G acylase (EC 3.5.1.11) from Escherichia coli catalyzed the synthesis of various beta-lactam antibiotics in ice at -20 degrees C with higher yields than obtained in solution at 20 degrees C. The initial ratio between aminolysis and hydrolysis of the acyl-enzyme complex in the synthesis of cephalexin increased from 1.3 at 20 degrees C to 25 at -20 degrees C. The effect on the other antibiotics studied was less, leading us to conclude that freezing of the reaction medium influences the hydrolysis of each nucleophile-acyl-enzyme complex to a different extent. Only free penicillin-G acylase could perform transformations in frozen media: immobilized preparations showed a low, predominantly hydrolytic activity under these conditions.
van Langen
L M
LM
Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Delft, The Netherlands.
de Vroom
E
E
van Rantwijk
F
F
Sheldon
R
R
D000658:Amoxicillin / Q000138:chemical synthesis / Q000378:metabolism; D000667:Ampicillin / Q000138:chemical synthesis / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism; D002434:Cefadroxil / Q000138:chemical synthesis / Q000378:metabolism; D002506:Cephalexin / Q000138:chemical synthesis / Q000378:metabolism; D004800:Enzymes, Immobilized / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D005615:Freezing; D010399:Penicillin Amidase / Q000737:chemistry* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004800:Enzymes, Immobilized; D002434:Cefadroxil; D000667:Ampicillin; D000658:Amoxicillin; D010399:Penicillin Amidase; D002506:Cephalexin