Biotechnological advances on Penicillin G acylase: Pharmaceutical implications,unique expression mechanism and production strategies |
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Authors: | Kajan Srirangan Valerie Orr Lamees Akawi Adam Westbrook Murray Moo-Young C. Perry Chou |
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Affiliation: | Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada |
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Abstract: | In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis.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. |
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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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