Improving phytase enzyme activity in a recombinant phyA mutant phytase from Aspergillus niger N25 by error-prone PCR

Appl Biochem Biotechnol. 2012 Feb;166(3):549-62. doi: 10.1007/s12010-011-9447-0. Epub 2011 Nov 19.

Abstract

The mutant acid phytase (phyA ( m )) gene was modified by random mutagenesis to improve enzymatic activity by using an error-prone PCR (ep-PCR) strategy. The mutated gene was linearized and inserted into plasmid vector pPIC9K and transformed by electroporation into Pichia pastoris GS115. A single transformant, PP-NP(ep)-6A, showing the strongest phytase activity from among the 5,500 transformants, was selected for detailed analyses. Southern blot analysis of the mutant yeast transformant showed that phyA ( ep ) gene was integrated into the chromosome genome through single crossover with one copy of phyA. The kinetic parameters indicated that the mutant one showed 61% higher specific activity and 53% lower k (m) value than that of PP-NP(m)-8 (P < 0.05). In addition, the overall catalytic efficiency (k (cat)/k (m)) of the mutant one was 84% higher (P < 0.05) than that of PP-NP(m)-8. Nine bases were altered in the mutant sequences, which resulted in three amino acid changes, namely, Glu156Gly, Thr236Ala, and Gln396Arg. The structural predictions indicated that the mutations generated by ep-PCR somehow reorganized or remodeled the active site, which could lead to increasing catalytic efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Phytase / chemistry
  • 6-Phytase / genetics
  • 6-Phytase / metabolism*
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Aspergillus niger / enzymology*
  • Aspergillus niger / genetics
  • Biocatalysis
  • Catalytic Domain
  • Electroporation
  • Escherichia coli
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genome, Fungal
  • Genomic Library
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Pichia / enzymology
  • Pichia / genetics*
  • Polymerase Chain Reaction
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity

Substances

  • Fungal Proteins
  • Recombinant Proteins
  • 6-Phytase