Process for producing peptides in E. coli

A process for the production of a (target peptide) comprising:

• A) culturing E. coli host cells transformed with a plasmid capable of expressing a gene coding for a fusion protein represented by the following formula:
• A--L--B
• wherein, B is a target peptide selected from the group consisting of calcitonin precursor, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide, A is a protective peptide comprising a fragment of 90-210 amino acids from the N-terminal of the E. coli .beta.-galactosidase polypeptide to protect the peptide to which it is fused, and L is a linker peptide positioned between the C-terminal of said protective peptide and the N-terminal of said target peptide and is selected such that when said fusion protein is treated with an enzyme or chemical substance, said target peptide is cleaved from said linker peptide, and wherein the isoelectric point of the entire fusion protein A--L--B is adjusted to a range between 4.9 and 6.9 by including a linker peptide having basic amino acid residues;
• B) obtaining an insoluble fraction comprising inclusion bodies by homogenization of said transformed E. coli host cells;
• C) solubilizing said fusion protein comprised in said inclusion bodies by treatment of said insoluble fraction with a solubilizing agent;
• and,
• D) cleaving the peptide bond between the C-terminal of the linker amino acid residue and the N-terminal of the target peptide contained in said solubilized fusion protein to release said target peptide from said fusion peptide.