Expression and purification of a novel single-chain diabody (scDb-hERG1/β1) from Pichia pastoris transformants

Protein Expr Purif. 2021 Aug:184:105879. doi: 10.1016/j.pep.2021.105879. Epub 2021 Apr 4.

Abstract

In the last decades, protein engineering has developed particularly in biotechnology and pharmaceutical field. In particular, the engineered antibody subclass has arisen. The single chain diabody format (scDb), conjugating small size with antigen specificity, offers versatility representing a gold standard for a variety of applications, spacing from research to diagnostics and therapy. Along with such advantages, comes the challenge of optimizing their production, improving expression systems, purification procedures and stability. All such parameters are detrimental for protein production in general and above all for recombinant antibody expression, which has to be fine-tuned, choosing a proper protein-expression host and adjusting expression protocols accordingly. In the present paper, we present data regarding the production and purification of a single chain diabody directed against the macromolecular complex hERG1/β1 integrin. We focus on the expression of clones deriving from the transformation of Pichia pastoris yeast cells. In particular, we compare two different clones arose from two separate transformation processes, demonstrating that both are suitable for proper protein expression. Moreover, we have set up an expression protocol and compared the yields obtained using two purification machines: Akta Pure and Akta Start, with a positive outcome.

Keywords: Affinity chromatography; Protein purification; Recombinant antibodies; Secreted proteins; Yeast protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ether-A-Go-Go Potassium Channels* / antagonists & inhibitors
  • Ether-A-Go-Go Potassium Channels* / chemistry
  • Gene Expression*
  • Humans
  • Integrin beta1* / chemistry
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Saccharomycetales* / genetics
  • Saccharomycetales* / metabolism
  • Single-Chain Antibodies* / biosynthesis
  • Single-Chain Antibodies* / chemistry
  • Single-Chain Antibodies* / genetics
  • Single-Chain Antibodies* / isolation & purification

Substances

  • Ether-A-Go-Go Potassium Channels
  • Integrin beta1
  • Itgb1 protein, human
  • KCNH1 protein, human
  • Recombinant Proteins
  • Single-Chain Antibodies

Supplementary concepts

  • Komagataella pastoris