Artificial signal peptide for expressing an insoluble protein as a soluble active form

Abstract

The present invention relates to expression vectors and methods for enhancing soluble expression and secretion of an insoluble heterologous protein, particularly a bulky folded active heterologous protein which has one or more transmembrane-like domains or intramolecular disulfide bonds by linking a leader peptide with acidic or basic pI and high hydrophilicity thereto; by substituting one or more amino acids within N-terminal of the heterologous protein with ones having acidic or neutral pI and high hydrophilicity; or reducing elevating ΔGvalue of a polynucleotide encoding the leader peptide having basic pI value and high hydrophilicity. The expression vector and the method may be used to produce of heterologous protein and to transduce of therapeutic proteins in a patient by preventing formation of insoluble inclusion body and by enhancing secretional efficiency of the heterologous protein into the periplasm or outside cell.