The use of highly expressed FTH1 as carrier protein for cytosolic targeting in Hansenula polymorpha

The iron storage protein ferritin is a member of the non-heme iron protein family. It can store and release iron, therefore it prevents the cell from damage caused by iron-dioxygen reactions as well as it provides iron for biological processing. To study whether the human ferritin heavy chain (FTH1) can be expressed in Hansenula polymorpha, we integrated an expression cassette for FTH1 and analyzed the protein expression. We found very efficient expression of FTH1 and obtained yields up to 1.9 g/L under non-optimized conditions. Based on this result we designed a FTH1-PTH fusion protein to successfully express the parathyroid hormone fragment 1–34 (PTH) for the first time intracellular in H. polymorpha.

► FTH1 is highly expressed in Hansenula polymorpha.
► A FTH1 fusion protein with cytosolic targeting has also been highly expressed.
► The FTH1-PTH fusion protein showed increased solubility compared to FTH1 alone.
► No degradation of PTH occurred when fused C-terminally to FTH1.