Achieving unprecedented stability in lyophilized recombinase polymerase amplification with thermostable pyruvate kinase from Thermotoga maritima

J Biosci Bioeng. 2024 Jul;138(1):29-35. doi: 10.1016/j.jbiosc.2024.04.003. Epub 2024 May 7.

Abstract

Recombinase polymerase amplification (RPA) is an isothermal DNA amplification reaction at around 41 °C using recombinase (Rec), single-stranded DNA-binding protein (SSB), strand-displacing DNA polymerase (Pol), and an ATP-regenerating enzyme. Considering the onsite use of RPA reagents, lyophilized RPA reagents with long storage stability are highly desired. In this study, as one of the approaches to solve this problem, we attempted to use a thermostable pyruvate kinase (PK). PK gene was isolated from a thermophilic bacterium Thermotoga maritima (Tma-PK). Tma-PK was expressed in Escherichia coli and purified from the cells. Tma-PK exhibited higher thermostability than human PK. The purified Tma-PK preparation was applied to RPA as an ATP-regenerating enzyme. Liquid RPA reagent with Tma-PK exhibited the same performance as that with human PK. Lyophilized RPA reagent with Tma-PK exhibited higher performance than that with human PK. Combined with our previous results of RPA reagents of thermostable Pol from a thermophilic bacterium, Aeribacillus pallidus, the results in this study suggest that thermostable enzymes are preferable to mesophilic ones as a component in lyophilized RPA reagents.

Keywords: Isothermal DNA amplification; Pyruvate kinase; Recombinase polymerase amplification; Thermostable enzyme.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Enzyme Stability*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Freeze Drying*
  • Humans
  • Nucleic Acid Amplification Techniques* / methods
  • Pyruvate Kinase* / chemistry
  • Pyruvate Kinase* / genetics
  • Pyruvate Kinase* / metabolism
  • Recombinases / chemistry
  • Recombinases / genetics
  • Recombinases / metabolism
  • Thermotoga maritima* / enzymology
  • Thermotoga maritima* / genetics

Substances

  • Pyruvate Kinase
  • Recombinases
  • DNA-Directed DNA Polymerase
  • Bacterial Proteins