Secretion of human growth hormone by the food-grade bacterium Staphylococcus carnosus requires a propeptide irrespective of the signal peptide used

Staphylococcal exoproteins can be divided into two groups. One group compri ses proteins bearing only a signal peptide, the other group requires an add itional propeptide for secretion. The secretion signals of the propeptide-r equiring lipase from Staphylococcus hyicus (Lip) have been frequently used to produce recombinant secretory proteins in the food-grade species Staphyl ococcus carnosus. However, it has been unclear whether recombinant proteins can be secreted using signal peptides of staphylococcal proteins without p ropeptide. The human growth hormone protein (hGH) was fused to various stap hylococcal secretion signals of proteins without propeptide (Seb, SceA, and SceB) and of proteins requiring a propeptide (lipase, lysostaphin, and gly cerol ester hydrolase), Secretory hGH was efficiently produced by S. carnos us after fusion with any propeptide-containing secretion signal, whereas pr ecursor proteins were retained in the cells when only a signal peptide was used. Addition of the first sis amino acid residues of mature SceA to the s ignal peptide did also not lead to secretion of hGH. It was concluded that the properties of the mature protein domains determine whether a propeptide is required for secretion or not. The Lip propeptide could be efficiently removed from hGH after introduction of an enterokinase cleavage site betwee n the two protein domains.