High-level secretory expression of recombinant type III human-like collagen α1 in Pichia pastoris via multilevel systematic optimization

Int J Biol Macromol. 2025 Jun:313:144270. doi: 10.1016/j.ijbiomac.2025.144270. Epub 2025 May 15.

Abstract

Collagen is the main component that makes up the internal structure of animals and is extensively used in several industrial fields including food, materials, chemicals, and pharmaceuticals. Despite the variety of preparation methods available, there is significant potential for enhancing the yield of recombinant collagen produced through engineered Pichia pastoris (P. pastoris). Increasing the copy number of the recombinant type III human collagen α1 (hlCOLIII) gene to improve the level of expression of the recombinant protein and co-expression of molecular chaperones to alleviate the resulting endoplasmic reticulum stress further promotes hlCOLIII secretion. By optimizing transcription driven by the AOX1 promoter and improving translation efficiency, a strain of P. pastoris expressing hlCOLIII efficiently was constructed, achieving a yield of 10.3 g/L in a 5 L fermenter. Further, hlCOLIII demonstrated notable antioxidant capacity and performed well in bioactivity analyses, including cell proliferation, migration, and adhesion. This study lays a solid foundation for the scalable industrial production of recombinant collagen and opens new avenues for its exploration in advanced biomedical materials.

Keywords: Efficient expression; Evaluations; Human-like collagen; Pichia pastoris.

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen Type III* / biosynthesis
  • Collagen Type III* / genetics
  • Collagen Type III* / metabolism
  • Collagen Type III* / pharmacology
  • Gene Expression*
  • Humans
  • Pichia* / genetics
  • Pichia* / metabolism
  • Recombinant Proteins* / biosynthesis
  • Recombinant Proteins* / genetics
  • Recombinant Proteins* / metabolism
  • Recombinant Proteins* / pharmacology
  • Saccharomycetales* / genetics
  • Saccharomycetales* / metabolism

Substances

  • Recombinant Proteins
  • Collagen Type III
  • Antioxidants

Supplementary concepts

  • Komagataella pastoris