Evaluation of Methylotrophic Yeast Ogataea thermomethanolica TBRC 656 as a Heterologous Host for Production of an Animal Vaccine Candidate

Mol Biotechnol. 2022 Nov;64(11):1288-1302. doi: 10.1007/s12033-022-00508-x. Epub 2022 May 20.

Abstract

Multiple yeast strains have been developed into versatile heterologous protein expression platforms. Earlier works showed that Ogataea thermomethanolica TBRC 656 (OT), a thermotolerant methylotrophic yeast, can efficiently produce several industrial enzymes. In this work, we demonstrated the potential of this platform for biopharmaceutical manufacturing. Using a swine vaccine candidate as a model, we showed that OT can be optimized to express and secrete the antigen based on porcine circovirus type 2d capsid protein at a respectable yield. Crucial steps for yield improvement include codon optimization and reduction of OT protease activities. The antigen produced in this system could be purified efficiently and induce robust antibody response in test animals. Improvements in this platform, especially more efficient secretion and reduced extracellular proteases, would extend its potential as a competitive platform for biopharmaceutical industries.

Keywords: Heterologous expression; Methylotrophic yeast; Ogataea thermomethanolica; Porcine circovirus type 2; Veterinary vaccine.

MeSH terms

  • Animals
  • Biological Products* / metabolism
  • Capsid Proteins / metabolism
  • Circovirus*
  • Peptide Hydrolases / metabolism
  • Saccharomycetales* / genetics
  • Saccharomycetales* / metabolism
  • Swine

Substances

  • Biological Products
  • Capsid Proteins
  • Peptide Hydrolases

Supplementary concepts

  • Ogataea thermomethanolica