A Systematic Review of the Potential of Pichia pastoris (Komagataella phaffii) as an Alternative Host for Biologics Production

The methylotrophic yeast Pichia pastoris is garnering interest as a chassis cell factory for the manufacture of recombinant proteins because it effectively satisfies the requirements of both laboratory and industrial set up. The optimisation of P. pastoris cultivation is still necessary due to strai...

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Bibliographic Details
Published in:Molecular biotechnology Vol. 66; no. 7; pp. 1621 - 1639
Main Authors: Vijayakumar, Vijay Elakkya, Venkataraman, Krishnan
Format: Journal Article
Language:English
Published: New York Springer US 01.07.2024
Springer Nature B.V
Subjects:
alternative hosts
Biochemistry
Biological Products - metabolism
Biological Techniques
Biotechnology
Cell Biology
Chemistry
Chemistry and Materials Science
CRISPR
CRISPR-Cas Systems
Gene dosage
Genetic diversity
Genetic engineering
Genetic Engineering - methods
Human Genetics
Komagataella pastoris
manufacturing
Methanol
peptides
Pichia
Pichia - genetics
Pichia - metabolism
Pichia pastoris
Process engineering
Protein engineering
Protein Science
Proteins
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Review
Saccharomycetales - genetics
Saccharomycetales - metabolism
Systematic review
therapeutics
Yeast
yeasts
2A peptide system
Proteolysis
Secretion
Recombinant proteins
CRISPR/Cas
Promoters
Codon optimization
Pichia pastoris
ISSN:1073-6085, 1559-0305, 1559-0305
Online Access:Get full text
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Summary:The methylotrophic yeast Pichia pastoris is garnering interest as a chassis cell factory for the manufacture of recombinant proteins because it effectively satisfies the requirements of both laboratory and industrial set up. The optimisation of P. pastoris cultivation is still necessary due to strain- and product-specific problems such as promoter strength, methanol utilisation type, and culturing conditions to realize the high yields of heterologous protein(s) of interest. Techniques integrating genetic and process engineering have been used to overcome these problems. Insight into the Pichia as an expression system utilizing MUT pathway and the development of methanol free systems are highlighted in this systematic review. Recent developments in the improved production of proteins in P. pastoris by (i) diverse genetic engineering such as codon optimization and gene dosage; (ii) cultivating tactics including co-expression of chaperones; (iii) advances in the use of the 2A peptide system, and (iv) CRISPR/Cas technologies are widely discussed. We believe that by combining these strategies, P. pastoris will become a formidable platform for the production of high value therapeutic proteins. Graphical Abstract
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ISSN:1073-6085
1559-0305
1559-0305
DOI:10.1007/s12033-023-00803-1