Hansenula polymorpha, also known as Pichia angusta, with its metabolism highly dependent on methanol as a carbon source, has been excessively employed in the production of therapeutic proteins for the last two decades. The yeast was first discovered in 1950s in spoiled orange juice.

Image source:

http://www.drugdevelopment-technology.com/contractors/contract_research/artes/

The biotechnological interest in Hansenula is mainly attributed to its unique capabilities underlied by its rare characteristics. For instance, being one of the limited group of yeast that are able to assimilate methanol, gives it the advantage of being able to utilize relatively cheap substrates. In addition, Upon high temperature,  Hansenula polymorpha shifts its biochemical methanol metabolism pathway to the biosynthesis of trehalose which is a thermo-protective sugar, this fact explains its unique ability to resist temperatures up to 49 degree Celsius. further, Hansenula is able to secrete the protein products directly to the culture, a fact that renders the whole process of downstream processing easier and less costly. finally, the ability to survive in wide pH range,from 2.5 to 6.5, makes it a versatile protein factory which is exploited in the production of various types proteins, each of which requires a very different optimum pH value throughout the fermentation process.

Image source:

http://en.wikipedia.org/wiki/Hansenula_polymorpha

( Budding Hansenula cells)

However, with Hansenula polymorpha post-translational modification processes are not highly regulated, this makes Hansenula useful for the production of relatively small to medium sized polypeptides as Parathyroid hormone, Staphylokinase, Elafin……etc.  However, Regarding large polypeptides, mammalian cells with tightly regulated post-translational modification processes represent a better option.

On the industrial scale, different strains of Hansenula polymorpha are being exploited as expression systems. For instance, a genetically engineered strain known as super-transformed strain bearing additional two advantages than the wild type strain. Being super-transformed means that it is capable of secreting Calnexin which is a protein Chaperone that functions to ensure proper folding of the secreted protein. Additionally, Calnexin enhances the protein secretion efficiency of Hansenula . Accordingly, the super-transformed strain gains its industrial potential in terms of quality assurance of the secreted protein product as well as increasing the  cost effectiveness of the industrial process.

References: 1.“Hansenula polymorpha” wikipedia, www.wikipedia.org

2. Gellissen G, “Hansenula ploymorpha : Biology & Applications”, 2002

3.Marcos A. Oliveira, Victor Genu, Anita P.T. Salmazo, Dirce M. Carraro and Gonçalo A.G. Pereira1 ”The transcription factor Snf1p is involved in a Tup1p-independent manner in the glucose regulation of the major methanol metabolism genes of HansenulaPolymorpha”, Genetics and Molecular Biology, 521-528 (2003)

Tags: Calnexin, Chaperone, Downstream processing, Elafin, Hansenula polymorpha, methanol, Parathyroid hormone, Post-translational modification, Staphylokinase, Super-transformed, Therapeutic proteins, thermo-protective, trehalose, Yeast