Basic leucine zipper transcription activators – tools to improve production and quality of human erythropoietin in Nicotiana benthamiana

Biotechnology Journal, vol. 19, pp. e2300715

Abstract

Human erythropoietin (hEPO) is one of the most in-demand biopharmaceuticals, however, its production is challenging. When produced in a plant expression system, hEPO results in extensive plant tissue damage and low expression. It is demonstrated that the modulation of the plant protein synthesis machinery enhances hEPO production. Co-expression of basic leucine zipper transcription factors with hEPO prevents plant tissue damage, boosts expression, and increases hEPO solubility. bZIP28 co-expression up-regulates genes associated with the unfolded protein response, indicating that the plant tissue damage caused by hEPO expression is due to the native protein folding machinery being overwhelmed and that this can be overcome by co-expressing bZIP28.

Authors 7

1. Nazgül Wagner Aachen Institute for Molecular Biotechnology

   RWTH Aachen University · Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Institute for Molecular Biotechnology RWTH Aachen University Aachen Germany

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA

   Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany

2. Konstantin Musiychuk

   Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA

3. Yôko Shôji

   Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA

4. Stephen Tottey

   Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA

5. Stephen J. Streatfield corresponding

   Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA

6. Rainer Fischer Aachen Institute for Molecular Biotechnology

   RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Biotechnology RWTH Aachen University Aachen Germany

   Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany

7. Vidadi Yusibov

   Fraunhofer USA

   Affiliation as printed

   Biotechnology Division Fraunhofer USA Inc., Center Mid‐Atlantic Newark Delaware USA

   Biotechnology Division, Fraunhofer USA Inc., Center Mid-Atlantic, Newark, Delaware, USA