A new role for penicillin acylases: degradation of acyl homoserine lactone quorum sensing signals by Kluyvera citrophila penicillin G acylase

Enzyme Microb Technol. 2014 Mar 5:56:1-7. doi: 10.1016/j.enzmictec.2013.12.010. Epub 2013 Dec 19.

Abstract

Use of penicillin acylases for the production of semi-synthetic penicillins is well-known. Escherichia coli penicillin G acylase (EcPGA) has been extensively used for this purpose; however, Kluyvera citrophila penicillin G acylase (KcPGA) is assumed to be a better substitute, owing to its increased resilience to extreme pH conditions and ease of immobilization. In the present article we report a new dimension for the amidase activity of KcPGA by demonstrating its ability to cleave bacterial quorum sensing signal molecules, acyl homoserine lactones (AHL) with acyl chain length of 6-8 with or without oxo-substitution at third carbon position. Initial evidence of AHL degrading capability of KcPGA was obtained using CV026 based bioassay method. Kinetic studies performed at pH 8.0 and 50 °C revealed 3-oxo-C6 HSL to be the best substrate for the enzyme with V(max) and K(m) values of 21.37+0.85 mM/h/mg of protein and 0.1+0.01 mM, respectively. C6 HSL was found to be the second best substrate with V(max) and K(m) value of 10.06+0.27 mM/h/mg of protein and 0.28+0.02 mM, respectively. Molecular modeling and docking studies performed on the active site of the enzyme support these findings by showing the fitting of AHLs perfectly within the hydrophobic pocket of the enzyme active site.

Keywords: Acyl homoserine lactones; CV026; KcPGA; Quorum quenching.

MeSH terms

  • Acyl-Butyrolactones / metabolism*
  • Amidohydrolases / metabolism
  • Amino Acid Motifs
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Catalytic Domain
  • Chromobacterium / metabolism
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Genes, Bacterial
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Kluyvera / enzymology*
  • Kluyvera / genetics
  • Models, Molecular
  • Penicillin Amidase / chemistry
  • Penicillin Amidase / genetics
  • Penicillin Amidase / physiology*
  • Penicillins / metabolism
  • Protein Conformation
  • Quorum Sensing / physiology*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Temperature

Substances

  • Acyl-Butyrolactones
  • Bacterial Proteins
  • Penicillins
  • Recombinant Fusion Proteins
  • Amidohydrolases
  • Penicillin Amidase