Protein Targeting Signals and Strategies for Pichia pastoris

Besides the simplicity of genetic modification and convenient low-effort cultivation, Pichia pastoris (today mostly Komagataella phaffii species are used for biotechnology) comes with another great advantage: simple targeting of recombinant proteins to different compartments of the host cell. Indeed, the most prominent pathway for recombinant proteins is the secretory pathway, whereby the protein is guided through the endoplasmic reticulum (ER) and Golgi apparatus, resulting in secretion at the cell surface. Secreted proteins can be separated from the cells, forgoing expensive cell disruption and purification processes. However, there are further localization sites for recombinant proteins (e.g., mitochondria, nucleus, peroxisomes, vacuole, cytoplasmic membrane, cell wall, etc.), technologically relevant.