From: Post-production protein stability: trouble beyond the cell factory
Protein engineering strategy | Result | Protein | Reference |
---|---|---|---|
Improving protein folding during production | Â | Â | Â |
Cys→Ser point mutations | Reduced aggregation, enhanced proteolytic stability | bFGFa | [100] |
Point mutations in an hydrophobic stretch | Reduced aggregation | 11 beta-HSD1 | [101] |
Directed evolution/point mutations | Reduced aggregation | Cytochrome P450sca-2 | [102] |
Fusion of SUMO tag | Improved refolding | Fgf15 | [103] |
Polycationic amino acid tag fusion | Reduced aggregation | Candida antarctica lipase B | [104] |
Fusion to polylysines or polyarginines | Reduced aggregation | BPTI-22 | [105] |
Fusion to MBP | Reduced aggregation | Ribonuclease inhibitor | [106] |
Fusion to GrpE | Reduced aggregation | hIL-3 | [107] |
Fusion to NusA | Reduced aggregation, enhanced proteolytic stability | E8R viral protein | [108] |
Improving protein folding, stability and performance during administration | Â | Â | Â |
Single amino acid substitution | Inhibited oligomer formation; enhanced bioavailability | Insulin Aspart ® | [109] |
Single amino acid substitution | Improved folding | INF-β-1b (Betaferon ®) | [110] |
N-terminal peptide deletion | Enhanced stability | KGF | [111] |
Fusion with albumin | Extended half-life | Albinterferon α-2b | [76] |
Fusion with transferrin | Enhanced gastrointestinal adsorption | hGH | [75] |
Artificial consensus protein sequence | Enhanced activity | Interferon αcon-1 (Infergen ®) | [112] |
Fusion of a HIV Tat segment | Enhanced solubility | p53 | [113] |
Fusion of a HIV Tat protein and ODD | Enhanced stability and activity in hypoxic tumor cells | Casp-3 | [114] |
Fusion of a HIV Tat protein and sequence modification | Cell penetration and selective activation in HIV-infected cells | Casp-3 | [115] |
Ligand incorporation (mainly antibody fragments) | Enhanced stability and bioavailbility | IL-2 | [71] |