US EPA

1451417 

Journal Article 

Bioprocess engineering aspects of heterologous protein production in Pichia pastoris: A review 

Potvin, G; Ahmad, A; Zhang, Z 

2012 

Yes 

Biochemical Engineering Journal
ISSN: 1369-703X 

64 

91-105 

10.1016/j.bej.2010.07.017 

WOS:000304223100012 

Pichia pastoris is currently one of the most effective and
versatile systems for the expression of heterologous proteins. Its success is due to its powerful
methanol-inducible alcohol oxidase 1 (AOX1) promoter, capacity to perform post-translational
modifications and pathways leading to recombinant products secretion. Despite its advantages, P.
pastoris cultivation is plagued by high protease expression levels, high sensitivity to methanol
levels, nutrient-deficiency when grown on defined media, difficulties in systematic study due to
product-specific effects, and health and safety concerns associated with the storage of large
quantities of methanol. Difficulties also arise that are specific to the cultivation methods and
control strategies used. The present review discusses several bioprocess engineering aspects
related to P. pastoris cultivation, including the different promoters available, both
constitutive and inductive, on- and off-line process parameter monitoring methods, fed-batch and
continuous cultivation control strategies, proteolytic degradation of products and methods to
minimize associated yield reductions, and the different models devised to describe cell growth
and protein production. The economics of P. pastoris cultivation, through a case-study involving
recombinant phytase production, are also discussed. The study of yeast fermentation is currently
very dynamic, and P. pastoris is on its way towards becoming a standard expression system. (C)
2010 Elsevier B.V. All rights reserved. 

Continuous cultivation; Fed-batch cultivation; Fermentation; Pichia pastoris; Process modeling; Proteolytic degradation