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Biotechnological advances on Penicillin G acylase: Pharmaceutical implications,unique expression mechanism and production strategies
Authors:Kajan Srirangan  Valerie Orr  Lamees Akawi  Adam Westbrook  Murray Moo-Young  C. Perry Chou
Affiliation:Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
Abstract:In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis.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.
Keywords:6-APA, 6-aminopenicillianic acid   7-ACA, 7-aminocephalosporanic acid   7-ADCA, 7-amino-desacetoxycephalonsporic acid   AA, amino acid   AfPGA, PGA from A. faecalis   βLA, β-lactam antibiotics   BRP, bacteroicin release protein   CRP, cAMP receptor protein   D-(&minus  )-PGA, D-(&minus  )-phenylglycine amide   D-(&minus  )-PGM, D-(&minus  )-phenylglycine methyl ester   D-(&minus  )-HPGA, D-(&minus  )-4-hydroxyphenylglycine amide   D-(&minus  )-HPGM, D-(&minus  )-4-hydroxyphenylglycine methyl ester   DNA, deoxyribonucleic acid   DO, dissolved oxygen   DAO, D-amino acid oxidase   EcPGA, PGA from E. coli   GA, glutaryl acylase   HSP, heat-shock protein   IM, inner membrane   IPTG, isopropyl-β-D-thio-galactoside   KcPGA, PGA from K. cryocrescens   LL, leaderless   mRNA, messenger-RNA   Ntn, N-terminal nucleophilic   nt, nucleotides   OM, outer membrane   PAA, phenylacetic acid   PEG, polyethylene glycol   PenG, penicillin G   PG, peptidoglycan   PGA, penicillin G acylase   PrPGA, PGA from P. rettgeri   PVA, penicillin V acylase   RBS, ribosome binding site   RNA, ribonucleic acid   SSC, semisynthetic cephalosporins   SSP, semi-synthetic penicillin   (S/H), synthesis/hydrolysis   Tat, Twin-Arg translocation   TCA, tricarboxylic acid   TF, trigger factor   TFF-AMEC, tangential flow filtration anion-exchange membrane chromatography   tRNA, transfer-RNA   TtPGA, PGA from T. thermophiles
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