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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
Institution: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Abstract:In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis.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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