Genetic and other difference among various yeast system

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What are the main differences among various yeast system?

Saccharomyces cerevisiae is one of the best-characterized eukaryotes and most widely used host systems for biopharmaceutical production since the early days of genetic engineering and recombinant protein production.

Recently, nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, Yarrowia lipolytica, Schizosaccharomyces pombe, and Kluyveromyces lactis have been developed as alternative hosts for the production of recombinant proteins.

Here we summary the main differences among various yeast system.

Yeast speciesAttributes
Saccharomyces cerevisiaeFavorable public acceptance
GRAS status
The most well studied of simple eukaryotes
Amenable to both classical genetics and modern recombinant DNA techniques
Versatile vector systems (episomal, integrative, copy-number regulated) are available (Invitrogen)
A wide range of mutant strains
Well-established fermentation and downstream processing
Hypermannosylation with immunogenic terminal _-1,3-linked mannose residues
Genome sequencing: Reference strain S288C; 12 157 Kb (6273 ORFs); Accession number PRJNA128
Pichia pastorisGRAS status
Tightly regulated, methanol-inducible AOX promoters
A Crabtree-negative yeast allowing for high dilution rates and high biomass yields in fermentation processes
Can grow rapidly on inexpensive media at high cell densities (up to 150 g DCW L_1)
Integrated vectors developed that help genetic stability of the recombinant elements, even in continuous and large-scale fermentation processes
Well-established commercial vector systems and host strains (Invitrogen)
A lesser extent of hypermannosylation compared to S. cerevisiae; No terminal _-1,3-linked mannose residues
Genome sequencing: Reference strain GS115; 9216 Kb (5040 ORFs); Accession number PRJNA39439, PRJEA37871
Hansenula polymorphaGRAS status
polymorpha Stringently regulated strong promoters (MOX, FMDH, etc.)
A Crabtree-negative yeast allowing for high dilution rates and high biomass yields in fermentation processes
Stable, multicopy integration of foreign DNA into chromosomal locations
Thermotolerant (growth up to 45 _C), resistant to heavy metals and oxidative stress
Can assimilate nitrates
A lesser extent of hypermannosylation compared to S. cerevisiae; No terminal _-1,3-linked mannose residues
Genome sequencing: Reference strain DL1; 9056 Kb (5325 ORFs); Accession number PRJNA60503
Schizosaccharomyces pombeAn oleaginous yeast, based on its ability to accumulate large amounts of lipids
GRAS status
Can grow in hydrophobic environments, that is able to metabolize triglycerides, fatty acids, n-alkanes, and n-paraffins as carbon sources for the bioremediation of environments contaminated with oil spills
Can secrete a variety of proteins via cotranslational translocation and efficient secretion signal recognition similar to higher eukaryotes
Availability of a commercial expression kit (YEASTERN BIOTECH CO., LTD.)
Salt tolerance
A lesser extent of hypermannosylation compared to S. cerevisiae; a lack of the immunogenic terminal _-1,3-mannose linkages
Genome sequencing: Reference strain CLIB122; 20 503 Kb (7042 ORFs); Accession number PRJNA12414
Kluyveromyces lactisA Crabtree-negative yeast allowing for high dilution rates and high biomass yields in fermentation processes
Lactose-fermenting present in milk and whey, and the strong, lactose inducible LAC4 promoter
Very high cell density (> 100 g DCW L_1)
Able to use both integrative and episomal expression vectors
An available easy-to-use reagent kit for K. lactis protein expression (New England Biolabs)
Terminal N-acetylglucosamine and no mannose phosphate
Genome sequencing: Reference strain NRRL Y-1140; 10 689 Kb (5502 ORFs); Accession number PRJNA12377

Ref: Yeast synthetic biology for the production of recombinant therapeutic proteins

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