Your protein size by itself is not going to be problematic.  More likely you'll stumble over a problem related to the vast species boundary you're crossing, like folding, disulfide bond formation, proteolytic processing, post-translational additions or quarternary structure assembly.  Try to identify any important structures in your helminth protein and convince yourself that pichia knows how to make those. 

Dear

We have noted that Pichia pastoris is an established protein expression host mainly used for  industrial enzymes. 

Some resaerchers have published interesting papers about Pichia pastoris that you can check:

-Mudassar Ahmad et al;  Appl Microbiol Biotechnol. 2014; 98(12): 5301–5317. Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047484/

-Li, P., Anumanthan, A., Gao, XG. et al. Appl Biochem Biotechnol (2007) 142: 105. Expression of Recombinant Proteins in Pichia Pastoris

Good luck

Marius

Dear Alvaro

It is reported the expression of proteins of more than 3000 aa (~200 KDa) in Pichia pastoris, however, the expression of those high mass proteins is not trivial, and you will have problems of solubility.

You will need to carefully select the promoter and the signal peptide.

I attached a couple of references that you can check.

Best regards

https://www.ncbi.nlm.nih.gov/pubmed/9035408

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047484/

Thanks all for your answer

Dear John Schloendorn

I agree about the species boundary but we are thinking to do expression in Pichia based on our previous experience expressing similar helminth proteins in this heterologous host. We’ve got a bunch of proteins working so we expected the PTM made by Pichia to be enough (hopefully) to produce an active protein. The problem is that prediction programs were “predicting” insolubility, instability, prone to degradation and other not-looking-good features. Thanks a lot for your comments.

Dear Marius K. Somda

Thanks for the papers

Dear Jose Manuel Ageitos

Thanks for the number “~200 KDa”. This means that, as John Schloendorn said, the protein size by itself is not going to be problematic. And again, with respect to the solubility is predicted to be insoluble, and many other not promising things. Thanks also for the papers.

We have finally set aside the production of this protein since everything around warns of a risky project, thanks again for your help