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Biotechnol Adv. 2013 Dec;31(8):1319-32. doi: 10.1016/j.biotechadv.2013.05.006. Epub 2013 May 27.

Biotechnological advances on penicillin G acylase: pharmaceutical implications, unique expression mechanism and production strategies.

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Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address:


In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis. Traditional penicillin chemistry involves the use of hazardous chemicals and harsh reaction conditions for the production of semisynthetic derivatives and, therefore, is being displaced by the biosynthetic platform using enzymatic transformations. Penicillin G acylase (PGA) is one of the most relevant and widely used biocatalysts for the industrial production of β-lactam semisynthetic antibiotics. Accordingly, considerable genetic and biochemical engineering strategies have been devoted towards PGA applications. This article provides a state-of-the-art review in recent biotechnological advances associated with PGA, particularly in the production technologies with an emphasis on using the Escherichia coli expression platform.


(S/H); 6-APA; 6-aminopenicillianic acid; 7-ACA; 7-ADCA; 7-amino-desacetoxycephalonsporic acid; 7-aminocephalosporanic acid; AA; AfPGA; BRP; CRP; D-(−)-4-hydroxyphenylglycine amide; D-(−)-4-hydroxyphenylglycine methyl ester; D-(−)-HPGA; D-(−)-HPGM; D-(−)-PGA; D-(−)-PGM; D-(−)-phenylglycine amide; D-(−)-phenylglycine methyl ester; D-amino acid oxidase; DAO; DNA; DO; EcPGA; Escherichia coli; GA; HSP; IM; IPTG; Industrial enzyme; KcPGA; LL; N-terminal nucleophilic; Ntn; OM; PAA; PEG; PG; PGA; PGA from A. faecalis; PGA from E. coli; PGA from K. cryocrescens; PGA from P. rettgeri; PGA from T. thermophiles; PVA; PenG; Penicillin; Penicillin G acylase; Penicillin chemistry; Posttranslational processing; PrPGA; RBS; RNA; Recombinant protein; SSC; SSP; Semisynthetic antibiotics; TCA; TF; TFF-AMEC; Tat; TtPGA; Twin-Arg translocation; amino acid; bacteroicin release protein; cAMP receptor protein; deoxyribonucleic acid; dissolved oxygen; glutaryl acylase; heat-shock protein; inner membrane; isopropyl-β-D-thio-galactoside; leaderless; mRNA; messenger-RNA; nt; nucleotides; outer membrane; penicillin G; penicillin G acylase; penicillin V acylase; peptidoglycan; phenylacetic acid; polyethylene glycol; ribonucleic acid; ribosome binding site; semi-synthetic penicillin; semisynthetic cephalosporins; synthesis/hydrolysis; tRNA; tangential flow filtration anion-exchange membrane chromatography; transfer-RNA; tricarboxylic acid; trigger factor; β-lactam antibiotics; βLA

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