Skip to content
2000
Volume 21, Issue 19
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Penicillin G Acylase (PGA) has emerged as a critical biocatalyst in pharmaceutical sciences, exceeding its traditional role in penicillin synthesis. Despite its industrial significance, challenges, including substrate specificity, stability under industrial conditions, and efficiency in immobilization, persist. Engineering enhanced enzyme variants and developing advanced immobilization techniques along with process optimization shall be possible solutions to further improve reaction efficiency and scalability. Green chemistry integration can make PGA-based processes more sustainable. Moreover, the use of computational tools, including AI-driven optimization, can guide enzyme design and reaction condition refinement. A review synthesizing these advancements not only consolidates existing knowledge but also identifies opportunities for further innovation, ensuring the enzyme’s continued industrial and scientific relevance. The review discusses the structure and functionality of PGA, highlighting its diverse applications beyond penicillin production. Beyond antibiotic synthesis, PGA's usefulness extends to ester synthesis, resolving racemic mixtures and peptide bond formation, underlining its importance in various bioconversions and synthetic reactions. This adaptability is crucial for green chemistry, promoting sustainable practices in industrial processes. The kinetic parameters of PGA are discussed, providing insights into its operational efficiency. Despite its significant potential, PGA faces limitations in commercial applications, primarily due to stability issues under industrial conditions. Efforts to enhance PGA's stability, including engineering approaches, are explored to improve its industrial applicability. The review concludes by emphasizing PGA's role as a catalyst with vast implications in science and medicine, particularly in an era of rising antibiotic resistance. It underscores the enzyme's interconnected roles in production and therapeutics, its broad spectrum of applications, and the shift from traditional penicillin synthesis to broad-spectrum bioconversions. The scope of PGA engineering is also highlighted, indicating future directions for research and application in the pharmaceutical industry.

© 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808347794250102113721
2025-01-10
2025-06-26
The full text of this item is not currently available.

References

  1. BečkaS. ŠtěpánekV. VyasarayaniR.W. GrulichM. MaršálekJ. PlháčkováK. DobišováM. MarešováH. PlačkováM. ValešováR. PalyzováA. DatlaA. AsharT.K. KyslíkP. Penicillin G acylase from Achromobacter sp. CCM 4824.Appl. Microbiol. Biotechnol.20149831195120310.1007/s00253‑013‑4945‑3 23674150
    [Google Scholar]
  2. AbianO. GrazúV. HermosoJ. GonzálezR. GarcíaJ.L. Fernández-LafuenteR. GuisánJ.M. Stabilization of penicillin G acylase from Escherichia coli: site-directed mutagenesis of the protein surface to increase multipoint covalent attachment.Appl. Environ. Microbiol.20047021249125110.1128/AEM.70.2.1249‑1251.2004 14766616
    [Google Scholar]
  3. BushK. BradfordP.A. β-Lactams and β-Lactamase inhibitors: An overview.Cold Spring Harb. Perspect. Med.201668a02524710.1101/cshperspect.a025247 27329032
    [Google Scholar]
  4. Cobos-PucL. Rodríguez-HerreraR. Cano-CabreraJ.C. Aguayo-MoralesH. Silva-BelmaresS.Y. GallegosA.C.F. HernándezJ.L.M. Classical and new pharmaceutical uses of bacterial penicillin G acylase.Curr. Pharm. Biotechnol.202021428729710.2174/1389201020666191111151642 31713475
    [Google Scholar]
  5. GrulichM. BrezovskýJ. ŠtĿpánek, V.; Palyzová, A.; Kyslíková, E.; Kyslík, P. Resolution of α/β-amino acids by enantioselective penicillin G acylase from Achromobacter sp.J. Mol. Catal., B Enzym.201512224024710.1016/j.molcatb.2015.09.008
    [Google Scholar]
  6. SambyalK. SinghR.V. Exploitation of E. coli for the production of penicillin G amidase: A tool for the synthesis of semisynthetic β-lactam antibiotics.J. Genet. Eng. Biotechnol.202119115610.1186/s43141‑021‑00263‑7 34652570
    [Google Scholar]
  7. BranniganJ.A. DodsonG. DugglebyH.J. MoodyP.C.E. SmithJ.L. TomchickD.R. MurzinA.G. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation.Nature1995378655541641910.1038/378416a0 7477383
    [Google Scholar]
  8. McVeyC.E. WalshM.A. DodsonG.G. WilsonK.S. BranniganJ.A. Crystal structures of penicillin acylase enzyme-substrate complexes: Structural insights into the catalytic mechanism.J. Mol. Biol.2001313113915010.1006/jmbi.2001.5043 11601852
    [Google Scholar]
  9. AvinashV.S. PanigrahiP. ChandD. PundleA. SureshC.G. RamasamyS. Structural analysis of a penicillin V acylase from Pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity.J. Struct. Biol.20161932859410.1016/j.jsb.2015.12.008 26707624
    [Google Scholar]
  10. PolizziK.M. Chaparro-RiggersJ.F. Vazquez-FigueroaE. BommariusA.S. Structure‐guided consensus approach to create a more thermostable penicillin G acylase.Biotechnol. J.20061553153610.1002/biot.200600029 16892288
    [Google Scholar]
  11. KallenbergA.I. van RantwijkF. SheldonR.A. Immobilization of penicillin G acylase: The key to optimum performance.Adv. Synth. Catal.20053477-890592610.1002/adsc.200505042
    [Google Scholar]
  12. LingX.M. WangX.Y. MaP. YangY. QinJ.M. ZhangX.J. ZhangY.W. Covalent immobilization of penicillin G acylase onto Fe3O4@chitosan magnetic nanoparticles.J. Microbiol. Biotechnol.201626582983610.4014/jmb.1511.11052 26869599
    [Google Scholar]
  13. LiK. MohammedM.A.A. ZhouY. TuH. ZhangJ. LiuC. ChenZ. BurnsR. HuD. RusoJ.M. TangZ. LiuZ. Recent progress in the development of immobilized penicillin G acylase for chemical and industrial applications: A mini‐review.Polym. Adv. Technol.202031336838810.1002/pat.4791
    [Google Scholar]
  14. YiuH.H.P. WrightP.A. Enzymes supported on ordered mesoporous solids: A special case of an inorganic–organic hybrid.J. Mater. Chem.20051535-36369010.1039/b506090g
    [Google Scholar]
  15. LeeW.C. GuoS.H. A novel enzyme reactor using gluten membrane entrapping cell‐associated enzyme.Biotechnol. Bioeng.200176431131710.1002/bit.10100 11745158
    [Google Scholar]
  16. PanigrahiP. ChandD. MukherjiR. RamasamyS. SureshC.G. Sequence and structure-based comparative analysis to assess, identify and improve the thermostability of penicillin G acylases.J. Ind. Microbiol. Biotechnol.201542111493150610.1007/s10295‑015‑1690‑x 26419382
    [Google Scholar]
  17. ArroyoM. de la MataI. AcebalC. Pilar CastillónM. Biotechnological applications of penicillin acylases: State-of-the-art.Appl. Microbiol. Biotechnol.200360550751410.1007/s00253‑002‑1113‑6 12536249
    [Google Scholar]
  18. GrafkováJ. SobotkováL. Penicillin G acylase--synthesis, regulation, production.Ceska Slov. Farm.2002511610 11910744
    [Google Scholar]
  19. SioC.F. QuaxW.J. Improved β-lactam acylases and their use as industrial biocatalysts.Curr. Opin. Biotechnol.200415434935510.1016/j.copbio.2004.06.006 15358003
    [Google Scholar]
  20. BarendsT. YoshidaH. DijkstraB. Three-dimensional structures of enzymes useful for? -lactam antibiotic production.Curr. Opin. Biotechnol.200415435636310.1016/j.copbio.2004.06.009 15358004
    [Google Scholar]
  21. MarešováH. PlačkováM. GrulichM. KyslíkP. Current state and perspectives of penicillin G acylase-based biocatalyses.Appl. Microbiol. Biotechnol.20149872867287910.1007/s00253‑013‑5492‑7 24445920
    [Google Scholar]
  22. CalleriE. TemporiniC. MassoliniG. CaccialanzaG. Penicillin G acylase-based stationary phases: Analytical applications.J. Pharm. Biomed. Anal.200435224325810.1016/S0731‑7085(03)00587‑9 15063459
    [Google Scholar]
  23. OhB. KimK. ParkJ. YoonJ. HanD. KimY. Modifying the substrate specificity of penicillin G acylase to cephalosporin acylase by mutating active-site residues.Biochem. Biophys. Res. Commun.2004319248649210.1016/j.bbrc.2004.05.017 15178432
    [Google Scholar]
  24. WeiD.Z. YangL. Effects of ethylene glycol on the synthesis of ampicillin using immobilized penicillin G acylase.J. Chem. Technol. Biotechnol.200378443143610.1002/jctb.749
    [Google Scholar]
  25. DengS. MaX. SuE. WeiD. Efficient cascade synthesis of ampicillin from penicillin G potassium salt using wild and mutant penicillin G acylase from Alcaligenes faecalis.J. Biotechnol.201621914214810.1016/j.jbiotec.2015.12.034 26732414
    [Google Scholar]
  26. VolpatoG. RodriguesR.C. Fernandez-LafuenteR. Use of enzymes in the production of semi-synthetic penicillins and cephalosporins: Drawbacks and perspectives.Curr. Med. Chem.201017323855387310.2174/092986710793205435 20858215
    [Google Scholar]
  27. TishkovV.I. SavinS.S. YasnayaA.S. Protein engineering of penicillin acylase.Acta Nat. (Engl. Ed.)201023476110.32607/20758251‑2010‑2‑3‑47‑61 22649651
    [Google Scholar]
  28. AlkemaW.B.L. HensgensC.M.H. SnijderH.J. KeizerE. DijkstraB.W. JanssenD.B. Structural and kinetic studies on ligand binding in wild-type and active-site mutants of penicillin acylase.Protein Eng. Des. Sel.200417547348010.1093/protein/gzh057 15254299
    [Google Scholar]
  29. DugglebyH.J. TolleyS.P. HillC.P. DodsonE.J. DodsonG. MoodyP.C.E. Penicillin acylase has a single-amino-acid catalytic centre.Nature1995373651126426810.1038/373264a0 7816145
    [Google Scholar]
  30. YangD. LiuH. ShiJ. WangX. ZhangS. ZouH. JiangZ. Enhancing 6-APA productivity and operational stability of penicillin G acylase via rapid surface capping on commercial resins.Ind. Eng. Chem. Res.20165539102631027010.1021/acs.iecr.6b02866
    [Google Scholar]
  31. ColeM. Penicillins and other acylamino compounds synthesized by the cell-bound penicillin acylase of Escherichia coli.Biochem. J.1969115474775610.1042/bj1150747 4982418
    [Google Scholar]
  32. OspinaS. BarzanaE. RamírezO.T. López-MunguíaA. Effect of pH in the synthesis of ampicillin by penicillin acylase.Enzyme Microb. Technol.199619646246910.1016/S0141‑0229(96)00032‑4
    [Google Scholar]
  33. AdrianoW.S. FilhoE.H.C. SilvaJ.A. GiordanoR.L.C. GonçalvesL.R.B. Stabilization of penicillin G acylase by immobilization on glutaraldehyde-activated chitosan.Braz. J. Chem. Eng.200522452953810.1590/S0104‑66322005000400005
    [Google Scholar]
  34. ChandD. VarshneyN. RamasamyS. PanigrahiP. BranniganJ.A. WilkinsonA.J. SureshC.G. Structure mediation in substrate binding and post‐translational processing of penicillin acylases: Information from mutant structures ofKluyvera citrophila penicillin G acylase.Protein Sci.201524101660167010.1002/pro.2761 26243007
    [Google Scholar]
  35. HaqueM.A. NathN.D. JohnstonT.V. HarunaS. AhnJ. OvissipourR. KuS. Harnessing biotechnology for penicillin production: Opportunities and environmental considerations.Sci. Total Environ.202494617423610.1016/j.scitotenv.2024.174236 38942308
    [Google Scholar]
  36. RajendhranJ. GunasekaranP. Recent biotechnological interventions for developing improved penicillin G acylases.J. Biosci. Bioeng.200497111310.1016/S1389‑1723(04)70157‑7 16233581
    [Google Scholar]
  37. PrietoI. MartínJ. ArcheR. FernándezP. Pérez-ArandaA. BarberoJ.L. Penicillin acylase mutants with altered site-directed activity from Kluyvera citrophila.Appl. Microbiol. Biotechnol.199033555355910.1007/BF00172550 1366784
    [Google Scholar]
  38. AlkemaW.B.L. HensgensC.M.H. KroezingaE.H. de VriesE. FlorisR. van der LaanJ.M. DijkstraB.W. JanssenD.B. Characterization of the β-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies.Protein Eng. Des. Sel.2000131285786310.1093/protein/13.12.857 11239085
    [Google Scholar]
  39. WeiC.L. YangY.B. DengC.H. LiuW.C. HsuJ.S. LinY.C. LiawS.H. TsaiY.C. Directed evolution of Streptomyces clavuligerus deacetoxycephalosporin C synthase for enhancement of penicillin G expansion.Appl. Environ. Microbiol.200571128873888010.1128/AEM.71.12.8873‑8880.2005 16332884
    [Google Scholar]
  40. RoaA. CastillónM.P. GobleM.L. VirdenR. GarcíaJ.L. New insights on the specificity of penicillin acylase.Biochem. Biophys. Res. Commun.1995206262963610.1006/bbrc.1995.1089 7826381
    [Google Scholar]
  41. AdikaneH.V. ThakarD.M. Studies of penicillin g acylase immobilization using highly porous cellulose-based polymeric membrane.Appl. Biochem. Biotechnol.201016041130114510.1007/s12010‑009‑8686‑9 19484409
    [Google Scholar]
  42. PanX. XuL. LiY. WuS. WuY. WeiW. Strategies to improve the biosynthesis of β-lactam antibiotics by penicillin G acylase: Progress and prospects.Front. Bioeng. Biotechnol.20221093648710.3389/fbioe.2022.936487 35923572
    [Google Scholar]
  43. SriranganK. OrrV. AkawiL. WestbrookA. Moo-YoungM. ChouC.P. Biotechnological advances on Penicillin G acylase: Pharmaceutical implications, unique expression mechanism and production strategies.Biotechnol. Adv.20133181319133210.1016/j.biotechadv.2013.05.006 23721991
    [Google Scholar]
  44. ChenC.X. WuQ. LiuB.K. LvD.S. LinX.F. Anhydrous tert-pentanol as a novel media for the efficient enzymatic synthesis of amoxicillin.Enzyme Microb. Technol.200842760160710.1016/j.enzmictec.2008.02.002
    [Google Scholar]
  45. GiordanoR.C. RibeiroM.P.A. GiordanoR.L.C. Kinetics of β-lactam antibiotics synthesis by penicillin G acylase (PGA) from the viewpoint of the industrial enzymatic reactor optimization.Biotechnol. Adv.20062412741a10.1016/j.biotechadv.2005.05.00315990267
    [Google Scholar]
  46. ThomasA.H. BroadbridgeR.A. The nature of carbenicillin resistance in Pseudomonas aeruginosa.J. Gen. Microbiol.197270223124110.1099/00221287‑70‑2‑231 4624990
    [Google Scholar]
  47. Sáez-LlorensX. McCrackenG.H. Clinical pharmacology of antibacterial agents. Infectious Diseases of the Fetus and Newborn Infant.Elsevier20061223126710.1016/B0‑72‑160537‑0/50039‑6
    [Google Scholar]
  48. PatelJ.A. JaviyaV.A. GhatakS.B. PatelK. Antibiotic susceptibility patterns of Pseudomonas aeruginosa at a tertiary care hospital in Gujarat, India.Indian J. Pharmacol.200840523023410.4103/0253‑7613.44156 20040963
    [Google Scholar]
  49. JagerS.A.W. ShapovalovaI.V. JekelP.A. AlkemaW.B.L. ŠvedasV.K. JanssenD.B. Saturation mutagenesis reveals the importance of residues αR145 and αF146 of penicillin acylase in the synthesis of β-lactam antibiotics.J. Biotechnol.20081331182610.1016/j.jbiotec.2007.08.039 17933411
    [Google Scholar]
  50. ElanderR.P. Industrial production of β-lactam antibiotics.Appl. Microbiol. Biotechnol.2003615-638539210.1007/s00253‑003‑1274‑y 12679848
    [Google Scholar]
  51. PapichM.G. Dicloxacillin Sodium. Saunders Handbook of Veterinary Drugs.Elsevier201623423510.1016/B978‑0‑323‑24485‑5.00205‑9
    [Google Scholar]
  52. ErarslanA. The hydrolysis of cephalosporin G by free and immobilized penicillin G acylsse from a mutant of Escherichia coli ATCC 11105.Process Biochem.199328531131810.1016/0032‑9592(93)85004‑Y
    [Google Scholar]
  53. VardanyanR.S. HrubyV. J. Antibiotics. Synthesis of Essential Drugs.Elsevier200642549810.1016/B978‑044452166‑8/50032‑7
    [Google Scholar]
  54. MaM. ChenX. YueY. WangJ. HeD. LiuR. Immobilization and property of penicillin G acylase on amino functionalized magnetic Ni0.3Mg0.4Zn0.3Fe2O4 nanoparticles prepared via the rapid combustion process.Front. Bioeng. Biotechnol.202311110882010.3389/fbioe.2023.1108820 36994365
    [Google Scholar]
  55. VélezA.M. da SilvaA.J. Luperni HortaA.C. SargoC.R. CampaniG. Gonçalves SilvaG. de Lima Camargo GiordanoR. ZangirolamiT.C. High-throughput strategies for penicillin G acylase production in rE. colifed-batch cultivations.BMC Biotechnol.2014141610.1186/1472‑6750‑14‑6 24444109
    [Google Scholar]
  56. IllanesA. ValenciaP. Industrial and therapeutic enzymes. Current Developments in Biotechnology and Bioengineering.Elsevier201726730510.1016/B978‑0‑444‑63662‑1.00013‑0
    [Google Scholar]
  57. WrightA.J. The penicillins.Mayo Clin. Proc.199974329030710.4065/74.3.290 10090000
    [Google Scholar]
  58. TorresR. de la MataI. CastillónM.P. ArroyoM. TorresJ. AcebalC. Purification and characterization of penicillin V acylase from Streptomyces lavendulae. Progress in Biotechnology; Elsevier, 19981571972410.1016/S0921‑0423(98)80109‑3
    [Google Scholar]
  59. AbianO. MateoC. Fernández-LorenteG. GuisánJ.M. Fernández-LafuenteR. Thermodynamically controlled synthesis of amide bonds catalyzed by highly organic solvent-resistant penicillin acylase derivatives.Biotechnol. Prog.200420111712110.1021/bp034266w 14763832
    [Google Scholar]
  60. NiersbachH. KühneA. TischerW. WeberM. WedekindF. PlappR. Improvement of the catalytic properties of penicillin G acylase from Escherichia coli ATCC 11105 by selection of a new substrate specificity.Appl. Microbiol. Biotechnol.199543467968410.1007/BF00164773 7546605
    [Google Scholar]
  61. AlkemaW.B.L. DijkhuisA.J. de VriesE. JanssenD.B. The role of hydrophobic active‐site residues in substrate specificity and acyl transfer activity of penicillin acylase.Eur. J. Biochem.200226982093210010.1046/j.1432‑1033.2002.02857.x 11985586
    [Google Scholar]
  62. GaborE.M. de VriesE.J. JanssenD.B. A novel penicillin acylase from the environmental gene pool with improved synthetic properties.Enzyme Microb. Technol.2005362-318219010.1016/j.enzmictec.2004.04.021
    [Google Scholar]
  63. CecchiniD.A. PavesiR. SannaS. DalyS. XaizR. PregnolatoM. TerreniM. Efficient biocatalyst for large-scale synthesis of cephalosporins, obtained by combining immobilization and site-directed mutagenesis of penicillin acylase.Appl. Microbiol. Biotechnol.20129561491150010.1007/s00253‑011‑3817‑y 22228258
    [Google Scholar]
  64. WangP. ZhangS. ZhangJ. ZhuY. Computational design of penicillin acylase variants with improved kinetic selectivity for the enzymatic synthesis of cefazolin.Biochem. Eng. J.202117510814910.1016/j.bej.2021.108149
    [Google Scholar]
  65. HeJ. HuangX. XueJ. ZhuY. Computational redesign of penicillin acylase for cephradine synthesis with high kinetic selectivity.Green Chem.201820245484549010.1039/C8GC03420F
    [Google Scholar]
  66. VerhaertR.M. RiemensA.M. van der LaanJ.M. van DuinJ. QuaxW.J. Molecular cloning and analysis of the gene encoding the thermostable penicillin G acylase from Alcaligenes faecalis.Appl. Environ. Microbiol.19976393412341810.1128/aem.63.9.3412‑3418.1997 9292993
    [Google Scholar]
  67. BrugginkA. RoosE.C. de VroomE. Penicillin acylase in the industrial production of β-lactam antibiotics.Org. Process Res. Dev.19982212813310.1021/op9700643
    [Google Scholar]
  68. ErarslanA. TerziI. GürayA. BermekE. Purification and kinetics of penicillin G acylase from a mutant strain of Escherichia coli ATCC 11105.J. Chem. Technol. Biotechnol.1991511274010.1002/jctb.280510103 1366868
    [Google Scholar]
  69. SuplatovD. PaninN. KirilinE. ShcherbakovaT. KudryavtsevP. ŠvedasV. Computational design of a pH stable enzyme: Understanding molecular mechanism of penicillin acylase’s adaptation to alkaline conditions.PLoS One201496e10064310.1371/journal.pone.0100643 24959852
    [Google Scholar]
  70. AbianO. MateoC. Fernández-LorenteG. PalomoJ.M. Fernández-LafuenteR. GuisánJ.M. Stabilization of immobilized enzymes against water-soluble organic cosolvents and generation of hyper-hydrophilic micro-environments surrounding enzyme molecules.Biocatal. Biotransform.2001195-648950310.3109/10242420108992032
    [Google Scholar]
  71. FerreiraA.L.O. GiordanoR.L.C. GiordanoR.C. Improving selectivity and productivity of the enzymatic synthesis of ampicillin with immobilized penicillin G acylase.Braz. J. Chem. Eng.200421451952910.1590/S0104‑66322004000400002
    [Google Scholar]
  72. KrzeslakJ. BraunP. VoulhouxR. CoolR.H. QuaxW.J. Heterologous production of Escherichia coli penicillin G acylase in Pseudomonas aeruginosa.J. Biotechnol.20091423-425025810.1016/j.jbiotec.2009.05.005 19481123
    [Google Scholar]
  73. van LangenL.M. van RantwijkF. ŠvedasV.K. SheldonR.A. Penicillin acylase-catalyzed peptide synthesis: A chemo-enzymatic route to stereoisomers of 3,6-diphenylpiperazine-2,5-dione.Tetrahedron Asymmetry20001151077108310.1016/S0957‑4166(00)00027‑6
    [Google Scholar]
  74. KheirolomoomA. ArdjmandM. FazeliniaH. ZakeriA. Clarification of penicillin G acylase reaction mechanism.Process Biochem.200136111095110110.1016/S0032‑9592(01)00145‑5
    [Google Scholar]
  75. PeiX. LuoZ. QiaoL. XiaoQ. ZhangP. WangA. SheldonR.A. Putting precision and elegance in enzyme immobilisation with bio-orthogonal chemistry.Chem. Soc. Rev.202251167281730410.1039/D1CS01004B 35920313
    [Google Scholar]
  76. BlumJ.K. DeagueroA.L. PerezC.V. BommariusA.S. Ampicillin synthesis using a two‐enzyme cascade with both α‐amino ester hydrolase and penicillin G acylase.ChemCatChem20102898799110.1002/cctc.201000135 22039394
    [Google Scholar]
  77. de SouzaV.R. SilvaA.C.G. PinottiL.M. AraújoH.S.S. GiordanoR. Characterization of the penicillin G acylase from Bacillus megaterium ATCC 14945. Braz. Arch. Biol. Technol.,200548spe10511110.1590/S1516‑89132005000400013
    [Google Scholar]
  78. MorillasM. McVEY, C.E.; Brannigan, J.A.; Ladurner, A.G.; Forney, L.J.; Virden, R. Mutations of penicillin acylase residue B71 extend substrate specificity by decreasing steric constraints for substrate binding.Biochem. J.2003371114315010.1042/bj20021383 12511194
    [Google Scholar]
  79. LvZ. WangZ. WuS. YuX. Enhanced catalytic performance of penicillin G acylase by covalent immobilization onto functionally-modified magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles.PLoS One2024191e029714910.1371/journal.pone.0297149 38241311
    [Google Scholar]
  80. BarberoJ. BuesaJ. de BuitragoG.G. MéndezE. Perez-ArandaA. GarcíaJ. Complete nucleotide sequence of the penicillin acylase gene from Kluyvera citrophila.Gene1986491698010.1016/0378‑1119(86)90386‑0 3032748
    [Google Scholar]
  81. MorleyK.L. KazlauskasR.J. Improving enzyme properties: When are closer mutations better?Trends Biotechnol.200523523123710.1016/j.tibtech.2005.03.005 15866000
    [Google Scholar]
  82. LiA. ChengC. QiW. PanX. XuX. WangX. WuC. ChuJ. HeB. Combing multiple site-directed mutagenesis of penicillin G acylase from Achromobacter xylosoxidans PX02 with improved catalytic properties for cefamandole synthesis.Int. J. Biol. Macromol.202117532232910.1016/j.ijbiomac.2021.01.194 33549660
    [Google Scholar]
  83. PanX. LiA. PengZ. JiX. ChuJ. HeB. Efficient synthesis of β-lactam antibiotics with in situ product removal by a newly isolated penicillin G acylase.Bioorg. Chem.20209910376510.1016/j.bioorg.2020.103765 32213361
    [Google Scholar]
  84. DengS. SuE. MaX. YangS. WeiD. Efficient enzymatic synthesis of ampicillin by mutant Alcaligenes faecalis penicillin G acylase.J. Biotechnol.2015199626810.1016/j.jbiotec.2015.01.004 25681630
    [Google Scholar]
  85. CaiG. ZhuS. YangS. ZhaoG. JiangW. Cloning, overexpression, and characterization of a novel thermostable penicillin G acylase from Achromobacter xylosoxidans: Probing the molecular basis for its high thermostability.Appl. Environ. Microbiol.20047052764277010.1128/AEM.70.5.2764‑2770.2004 15128530
    [Google Scholar]
  86. WangJ. ZhangQ. HuangH. YuanZ. DingD. YangS. JiangW. Increasing synthetic performance of penicillin G acylase from Bacillus megaterium by site-directed mutagenesis.Appl. Microbiol. Biotechnol.20077451023103010.1007/s00253‑006‑0752‑4 17186238
    [Google Scholar]
  87. XueP. GuY. SuW. ShuaiH. WangJ. In situ one-pot preparation of superparamagnetic hydrophilic porous microspheres for covalently immobilizing penicillin G acylase to synthesize amoxicillin.Appl. Surf. Sci.201636242743310.1016/j.apsusc.2015.11.209
    [Google Scholar]
  88. KubiakM. MayerJ. KampenI. SchildeC. BiedendieckR. Structure-properties correlation of cross-linked penicillin G acylase crystals.Crystals (Basel)202111445110.3390/cryst11040451
    [Google Scholar]
  89. BagherinejadM.R. KorbekandiH. TavakoliN. AbediD. Immobilization of penicillin G acylase using permeabilized Escherichia coli whole cells within chitosan beads.Res. Pharm. Sci.2012727985 23181084
    [Google Scholar]
  90. da RochaT.N. Morellon-SterllingR. Rocha-MartinJ. BolivarJ.M. GonçalvesL.R.B. Fernandez-LafuenteR. Immobilization of penicillin G acylase on vinyl sulfone-agarose: An unexpected effect of the ionic strength on the performance of the immobilization process.Molecules20222721758710.3390/molecules27217587 36364414
    [Google Scholar]
  91. McDonaldM.A. BommariusA.S. RousseauR.W. GroverM.A. Continuous reactive crystallization of β-lactam antibiotics catalyzed by penicillin G acylase. Part I: Model development.Comput. Chem. Eng.201912333134310.1016/j.compchemeng.2018.12.029
    [Google Scholar]
  92. MoserC. LercheC.J. ThomsenK. HartvigT. SchierbeckJ. JensenP.Ø. CiofuO. HøibyN. Antibiotic therapy as personalized medicine – general considerations and complicating factors.Acta Pathol. Microbiol. Scand. Suppl.2019127536137110.1111/apm.12951 30983040
    [Google Scholar]
  93. WichmannJ. MayerJ. HintmannM. LukatP. BlankenfeldtW. BiedendieckR. Multistep engineering of a penicillin G acylase for systematic improvement of crystallization efficiency.Cryst. Growth Des.20232353230324310.1021/acs.cgd.2c01408
    [Google Scholar]
  94. BahmanM. Characteristics of penicillin G acylase immobilized onto iron oxide nanoparticles.Br. Biotechnol. J.20133336737610.9734/BBJ/2013/2987
    [Google Scholar]
  95. SethR. MeenaA. Enzymes-based nanomaterial synthesis: An eco-friendly and green synthesis approach.Clean Technol. Environ. Policy202410.1007/s10098‑024‑02854‑7
    [Google Scholar]
  96. DeagueroA.L. BlumJ.K. BommariusA.S. Improving the diastereoselectivity of penicillin G acylase for ampicillin synthesis from racemic substrates.Protein Eng. Des. Sel.201225313514410.1093/protein/gzr065 22271751
    [Google Scholar]
  97. GrulichM. BrezovskýJ. ŠtěpánekV. PalyzováA. MarešováH. ZahradníkJ. KyslíkováE. KyslíkP. In-silico driven engineering of enantioselectivity of a penicillin G acylase towards active pharmaceutical ingredients.J. Mol. Catal., B Enzym.2016133S53S5910.1016/j.molcatb.2016.11.014
    [Google Scholar]
  98. Cerqueira PereiraS. BussamaraR. MarinG. Lima Camargo GiordanoR. DupontJ. de Campos GiordanoR. Enzymatic synthesis of amoxicillin by penicillin G acylase in the presence of ionic liquids.Green Chem.20121411314610.1039/c2gc36158b
    [Google Scholar]
/content/journals/lddd/10.2174/0115701808347794250102113721
Loading
/content/journals/lddd/10.2174/0115701808347794250102113721
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test