Construction of uricase-overproducing strains of Hansenula polymorpha and its application as biological recognition element in microbial urate biosensor

BMC Biotechnol. 2011 May 25:11:58. doi: 10.1186/1472-6750-11-58.

Abstract

Background: The detection and quantification of uric acid in human physiological fluids is of great importance in the diagnosis and therapy of patients suffering from a range of disorders associated with altered purine metabolism, most notably gout and hyperuricaemia. The fabrication of cheap and reliable urate-selective amperometric biosensors is a challenging task.

Results: A urate-selective microbial biosensor was developed using cells of the recombinant thermotolerant methylotrophic yeast Hansenula polymorpha as biorecognition element. The construction of uricase (UOX) producing yeast by over-expression of the uricase gene of H. polymorpha is described. Following a preliminary screening of the transformants with increased UOX activity in permeabilized yeast cells the optimal cultivation conditions for maximal UOX yield namely a 40-fold increase in UOX activity were determined.The UOX producing cells were coupled to horseradish peroxidase and immobilized on graphite electrodes by physical entrapment behind a dialysis membrane. A high urate selectivity with a detection limit of about 8 μM was found.

Conclusion: A strain of H. polymorpha overproducing UOX was constructed. A cheap urate selective microbial biosensor was developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques / methods*
  • Cloning, Molecular
  • Electrochemical Techniques / methods
  • Electrodes
  • Enzymes, Immobilized / chemistry
  • Enzymes, Immobilized / metabolism
  • Horseradish Peroxidase / chemistry
  • Horseradish Peroxidase / metabolism
  • Humans
  • Pichia / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Urate Oxidase / biosynthesis*
  • Urate Oxidase / genetics
  • Uric Acid / analysis*

Substances

  • Enzymes, Immobilized
  • Recombinant Proteins
  • Uric Acid
  • Horseradish Peroxidase
  • Urate Oxidase