Customized yeast cell factories for biopharmaceuticals: from cell engineering to process scale up

Abstract

The manufacture of recombinant therapeutics is a fastest-developing section of therapeutic pharmaceuticals and presently plays a significant role in disease management. Yeasts are established eukaryotic host for heterologous protein production and offer distinctive benefits in synthesising pharmaceutical recombinants. Yeasts are proficient of vigorous growth on inexpensive media, easy for gene manipulations, and are capable of adding post translational changes of eukaryotes. Saccharomyces cerevisiae is model yeast that has been applied as a main host for the manufacture of pharmaceuticals and is the major tool box for genetic studies; nevertheless, numerous other yeasts comprising Pichia pastoris, Kluyveromyces lactis, Hansenula polymorpha, and Yarrowia lipolytica have attained huge attention as non-conventional partners intended for the industrial manufacture of heterologous proteins. Here we review the advances in yeast gene manipulation tools and techniques for heterologous pharmaceutical protein synthesis. Application of secretory pathway engineering, glycosylation engineering strategies and fermentation scale-up strategies in customizing yeast cells for the synthesis of therapeutic proteins has been meticulously described.

A computational toolbox to investigate the metabolic potential and resource allocation in fission yeast

“…Lastly, recent studies suggested S. pombe could find novel applications in biotechnology, including winemaking (Benito et al, 2016) and flavour formation during food fermentations (Du et al, 2021), but also as a possible cell factory (Madhavan et al, 2021). S. pombe ’s ability to grow in environments with low water activity, high alcohol content, very low pH and a wide range of temperatures (Loira et al, 2018) make it an attractive, and perhaps underutilized, biotechnological tool.…”

Yarrowia lipolytica as an Alternative and Valuable Source of Nutritional and Bioactive Compounds for Humans

“…Y. lipolytica also has an operational secretory system with which it releases huge quantities of enzymes, such as lipases [ 196 ] and proteases [ 197 ], and heterologous proteins [ 27 , 198 , 199 , 200 , 201 , 202 ] for industrial applications. Among the more than 100 recombinant proteins produced by engineered Y. lipolytica [ 202 ], there are several pharmaceutically important human-compatible bio-compounds secreted by ‘humanized’ strains, including interferon alpha 2b [ 203 ], epidermal growth factor [ 204 ], N -glycoproteins [ 205 , 206 ], blood coagulation factor XIIIa [ 207 ], proinsulin and insulinotropin [ 208 ], cytochrome P450 [ 209 ], estrogen receptor α [ 210 ], and anaphylatoxin C5a that possesses both spasmogenic and leukocyte-related properties [ 211 ].…”

Current Status and Perspective on the Use of Viral-Based Vectors in Eukaryotic Microalgae

“…In biopharmaceutical terms, these molecules are specifically produced under biotechnological processes based on genetically engineered organisms used as an expression host [ 4 ]. The main organisms used here are bacteria, yeast, mammalian cells, and insect cells, with each system having their own advantages as well as limitations [ 5 , 6 , 7 , 8 ].…”