Use of Enzymes in the Production of Semi-Synthetic Penicillins and Cephalosporins: Drawbacks and Perspectives
In fact, the hydrolysis of penicillin G to produce 6-APA catalyzed by penicillin G acylase is one of the most successful historical examples of the enzymatic biocatalysis, and much effort has been devoted to find enzymatic routes to hydrolyze cephalosporin C. Initially this could be accomplished in a quite complex system, using a two enzyme system (D-amino acid oxidase plus glutaryl acylase), but very recently an efficient cephalosporin acylase has been designed by genetic tools. Other strategies, including metabolic engineering to produce other antibiotic nuclei, have been also reported.
Regarding the amidation step, much effort has been devoted to the improvement of penicillin acylases for these reactions since 1960. New reaction strategies, continuous product extraction or new penicillin acylases with better properties have proven to be the key to have competitive biocatalytic processes.
In this review, a critical discussion of these very interesting advances in the application of enzymes for the industrial synthesis of semi-synthetic antibiotics will be presented.
Keywords: Antibiotic synthesis; Cephalosporium acremo-nium; D-amino acid oxi-dase (DAAO); D-amino acid oxidase; Electrodialysis; Flomoxef; Immobilization; Oxycephams; Penicillium chrysogenum; Semi-synthetic -lactamic antibiotics; Streptomyces cla-vuligerus; a membrane reactor-separator; bioreactor; biotransformation; carboxylic acid; carboxylic moieties; cefalotin; cefamandol; cefazolin; cefonicid; cephalosporin C; cephalosporin acylase; cephalosporin hydrolysis; chemoenzyamtic route; crosslinked en-zyme aggregates; enzyme reaction design; glutarayl acylase; glutaryl acylase; glyoxyl-agarose; hydrophobicity; latamoxef; mutagenesis; penicillin G; penicillin G acylase; phenylacetic acid; phenylgly-cine methyl ester (PGM); phenylglycine
Document Type: Research Article
Publication date: 2010-11-01
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.