Enhanced soluble expression and effective purification of recombinant human interleukin-11 by SUMO fusion in Escherichia coli

Human interleukin-11 is a multifunctional cytokine applied for the clinical treatment of thrombocytopenia. However, IL-11 has been considered a difficult protein in to express in an Escherichia coli expression system. Here, we demonstrate a suitable construction for high production of recombinant human interleukin-11 (rhIL-11) in E. coli. An optimized codon gene encoding human IL-11 was inserted in-frame with the small ubiquitin like modifier (SUMO) protein in the pE-SUM03 vector. The SUMO_IL-11 fusion protein was entirely expressed in soluble form and reached 31.6% of total soluble protein in E. coli. The rhIL-11 protein with a purity of over 99% was obtained at high protein yields of 320 mg rhIL-11 per liter of bacterial culture. Bioactivity of rhIL-11, as determined by proliferation of a TF-1 cytokine-dependent cell line, was 4.17 x 10(5) unit/mg, similar to the activity of the natural protein. Interestingly, the rhIL-11 was purified easily and effectively due to its selective precipitation from the reaction mixture. To the best of our knowledge, this is the first report demonstrating self-aggregating recombinant protein after cleavage from SUMO. Thus, expression of rhIL-11 fused with SUMO yielded greatly increased soluble production and convenient purification, and could offer a potential drug candidate for deployment in clinical trials.