Yeast expression platform

Abstract: Yeast was the first microorganism used by mankind for biotransformation of feedstock that laid the foundations of industrial biotechnology. Long historical use, vast amount of data, and experience paved the way for Saccharomyces cerevisiae as a first yeast cell factory, and still it is an important expression platform as being the production host for several large volume products. Continuing special needs of each targeted product and different requirements of bioprocess operations have led to identification of different yeast expression systems. Modern bioprocess engineering and advances in omics technology, i.e., genomics, transcriptomics, proteomics, secretomics, and interactomics, allow the design of novel genetic tools with fine-tuned characteristics to be used for research and industrial applications. This chapter focuses on established and upcoming yeast expression platforms that have exceptional characteristics, such as the ability to utilize a broad range of carbon sources or remarkable resistance to various stress conditions. Besides the conventional yeast S. cerevisiae, established yeast expression systems including the methylotrophic yeasts Pichia pastoris and Hansenula polymorpha, the dimorphic yeasts Arxula adeninivorans and Yarrowia lipolytica, the lactose-utilizing yeast Kluyveromyces lactis, the fission yeast Schizosaccharomyces pombe, and upcoming yeast platforms, namely, Kluyveromyces marxianus, Candida utilis, and Zygosaccharomyces bailii, are compiled with special emphasis on their genetic toolbox for recombinant protein production.

Abstract: Although improvements in antibody expression by mammalian cells are nearing maturation, efforts to improve antibody efficacy through glycoengineering are rapidly expanding. For example, the production of full length monoclonal antibodies with uniform human N-linked glycans by glycoengineered yeast has been used to optimize antibody effector function. The glycoengineered yeast expression platform not only enables elucidation of structure function relationships but also offers a robust and economically viable alternative to mammalian cell expression. This chapter provides an overview of glycobiology, engineering of P. pastoris to secrete recombinant proteins with uniform human N-linked glycans as well as bioprocess considerations in the production of full length monoclonal antibodies by a yeast based expression system.