ARTES' strategy is optimizing a yeast production strain already displaying a very high productivity combined to the applicability to totally different recombinant proteins being expressed from an approved yeast expression platform. Hansenula and Arxula are getting another partner: Calnexin. Transferring the results from laboratory shake flasks to industrial scale fermentation, ARTES invented a tool to facilitate improvements at already high level coupled to broad application area.

Heterologous expression of commercially valuable proteins on an industrial
scale requires the ability to achieve high yields if commercial production of
the target protein is to be cost-effective. Standard strategies for achieving
this aim include different optimizations in the course of strain generation of
a particular production cell line. ARTES has elaborated an innovative genetically
manipulation setup to optimize a given yeast production strain in order
to enhance its productivity. The technology encompasses the introduction
of additional gene-copies of yeast Calnexin into the receiver's genome. This
specific research setup was evaluated with more than ten totally diverse
recombinant proteins of commercial interest in shake flasks as well as in pilot
fermentation scale. ARTES achieved two- to five fold boost of productivity on
proteins already secreted at g/L level before.

Yeast Calnexin represents the counterpart to the mammalian Calreticulin/
Calnexin chaperon system that plays a major role in quality control and
folding assistance of newly synthesised glycoproteins passing the ER. Recent
publications describe yeast Calnexin to act on a much broader subset of
substrates being finally assembled in the secretory pathway. Differentiating
the gene doses of Calnexin in yeasts may represent a core adjusting screw to
improve the capability of host cells to produce foreign proteins.

The fascinating benefit of this particular manipulation strategy is the opportunity
to optimize a yeast production strain already displaying a very high
productivity combined to the applicability to totally different recombinant
proteins being expressed from an approved yeast expression platform.
Together with the possibility to transfer the results from laboratory shake
flasks to industrial scale fermentation, ARTES invented a tool to facilitate
improvements at already high level coupled to broad application area.
A recently approved European patent and an actual publication support the
overproduction of yeast Calnexin for production strain engineering.

With the integration of high copy numbers of multiple expression cassettes
in one cell, Hansenula is the ideal host for such combinatory optimization
approaches. The research on secretion stimulating effects in Hansenula in
particular and in yeast in general is continued at ARTES' labs with work on
other chaperones.

In addition to Calnexin, ARTES offers exclusively an additional chaperone suitable as a secretion enhancer: SEB. This chaperone, another ER protein involved in protein translocation, is known to improve secretion in Saccharomyces twofold.