Non-conventional yeasts: Versatile platforms for the expression and secretion of eukaryotic proteins

The yeast, Saccharomyces cerevisiae, a model organism, has been extensively used for expressing proteins for industrial and biomedical applications. However, the protein secretion efficiency of the yeast is limited. This led to the investigation of the non-conventional yeast, Pichia pastoris, as an alternative. But this yeast also has limitations. In this review, we evaluate the potential of eight other non-conventional yeasts (NCYs), closely related to S. cerevisiae and P. pastoris, as platforms for expressing and secreting eukaryotic proteins. The NCYs, including Blastobotrys adeninivorans, Cyberlindnera jadinii, Debaryomyces hansenii, Kluyveromyces lactis, Kluyveromyces marxianus, Ogataea polymorpha, Scheffersomyces stipitis, and Yarrowia lipolytica, have unique metabolic pathways that enable the use of a broader set of substrates. They also have high tolerance for industrial conditions. These characteristics bring down the costs of production. Moreover, the available technologies for genome and metabolic editing and optimizing protein secretion pathways have helped increase the quality and quantity of protein yield from these NCYs. In this review, we present evidence from recent research that suggests that the selected NCYs can match or even surpass the yield of heterologous proteins, compared to S. cerevisiae and P. pastoris. We also highlight the potential for the further development of these NCYs by integrating insights into their biology with cutting-edge engineering strategies to create biotechnology for sustainable and cost-effective industrial protein production.