Multiply mutated Gaussia luciferases provide prolonged and intense bioluminescence

Biochem Biophys Res Commun. 2009 Nov 27;389(4):563-8. doi: 10.1016/j.bbrc.2009.09.006.

Abstract

Gaussia luciferase (GLuc) from the copepod Gaussia princeps is both the smallest and brightest known luciferase. GLuc catalyzes the oxidation of coelenterazine to produce an intense blue light but with a very short emission half-life. We report mutated GLucs with much longer luminescence half-lives that retain the same initial intensity as the wild-type enzyme. The GLuc variants were produced using cell-free protein synthesis to provide high yields and rapid production of fully active product as well as simple non-natural amino acid substitution. By incorporating homopropargylglycine and attaching PEG using azide-alkyne click reactions, we also show that the four methionines in GLuc are surface accessible. The mutants provide a significantly improved reporter protein for both in vivo and in vitro studies, and the successful non-natural amino acid incorporation and PEG attachment indicate the feasibility of producing useful bioconjugates using click attachment reactions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Copepoda / enzymology*
  • Luciferases / chemistry*
  • Luciferases / genetics
  • Luciferases / isolation & purification
  • Luminescence*
  • Molecular Sequence Data
  • Mutant Proteins / chemistry*
  • Mutant Proteins / genetics
  • Mutant Proteins / isolation & purification
  • Mutation

Substances

  • Mutant Proteins
  • Luciferases