Enzyme stabilization by domain insertion into a thermophilic protein

Protein Eng Des Sel. 2009 Oct;22(10):615-23. doi: 10.1093/protein/gzp044. Epub 2009 Jul 21.

Abstract

Insufficient kinetic stability of exoinulinase (EI) restricts its application in many areas including enzymatic transformation of inulin for production of ultra-high fructose syrup and oligofructan, as well as fermentation of inulin into bioethanol. The conventional method for enzyme stabilization involves mutagenesis and therefore risks alteration of an enzyme's desired properties, such as activity. Here, we report a novel method for stabilization of EI without any modification of its primary sequence. Our method employs domain insertion of an entire EI domain into a thermophilic scaffold protein. Insertion of EI into a loop of a thermophilic maltodextrin-binding protein from Pyrococcus furiosus (PfMBP) resulted in improvement of kinetic stability (the duration over which an enzyme remains active) at 37 degrees C without any compromise in EI activity. Our analysis suggests that the improved kinetic stability at 37 degrees C might originate from a raised kinetic barrier for irreversible conversion of unfolded intermediates to completely inactivated species, rather than an increased energy difference between the folded and unfolded forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus / enzymology
  • Aspergillus / genetics
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Enzyme Stability
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Glycoside Hydrolases / chemistry*
  • Glycoside Hydrolases / genetics
  • Glycoside Hydrolases / metabolism
  • Kinetics
  • Models, Molecular
  • Protein Engineering / methods*
  • Protein Folding
  • Protein Structure, Tertiary / genetics*
  • Pyrococcus / genetics
  • Pyrococcus / metabolism
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Temperature
  • Urea / chemistry

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Fungal Proteins
  • Recombinant Fusion Proteins
  • Urea
  • Glycoside Hydrolases
  • inulinase