Current achievements, strategies, obstacles, and overcoming the challenges of the protein engineering in Pichia pastoris expression system

• Published in: World journal of microbiology & biotechnology 2024-01, Vol.40 (1), p.39-39, Article 39
• Main Authors: Eskandari, Azadeh, Nezhad, Nima Ghahremani, Leow, Thean Chor, Rahman, Mohd Basyaruddin Abdul, Oslan, Siti Nurbaya
• Format: Article
• Language: English
• Subjects: Applied Microbiology; Biochemistry; Biomedical and Life Sciences; Biotechnology; Endoplasmic reticulum; Environmental Engineering/Biotechnology; Life Sciences; Microbiology; Molecular biology; Pichia - genetics; Pichia - metabolism; Pichia pastoris; Protein Engineering; Protein folding; Proteins; Recombinant Proteins - metabolism; Review; Saccharomyces cerevisiae - metabolism; Secretion; Signal peptidase; Yeast; Yeasts
• ISSN: 0959-3993; 1573-0972
• DOI: 10.1007/s11274-023-03851-6

Yeasts serve as exceptional hosts in the manufacturing of functional protein engineering and possess industrial or medical utilities. Considerable focus has been directed towards yeast owing to its inherent benefits and recent advancements in this particular cellular host. The Pichia pastoris expression system is widely recognized as a prominent and widely accepted instrument in molecular biology for the purpose of generating recombinant proteins. The advantages of utilizing the P. pastoris system for protein production encompass the proper folding process occurring within the endoplasmic reticulum (ER), as well as the subsequent secretion mediated by Kex2 as a signal peptidase, ultimately leading to the release of recombinant proteins into the extracellular environment of the cell. In addition, within the P. pastoris expression system, the ease of purifying recombinant protein arises from its restricted synthesis of endogenous secretory proteins. Despite its achievements, scientists often encounter persistent challenges when attempting to utilize yeast for the production of recombinant proteins. This review is dedicated to discussing the current achievements in the usage of P. pastoris as an expression host. Furthermore, it sheds light on the strategies employed in the expression system and the optimization and development of the fermentative process of this yeast. Finally, the impediments (such as identifying high expression strains, improving secretion efficiency, and decreasing hyperglycosylation) and successful resolution of certain difficulties are put forth and deliberated upon in order to assist and promote the expression of complex proteins in this prevalent recombinant host.