The general practice for producing a recombinant protein or peptide of interest (POI) starts by cloning the DNA sequence encoding the POI into a plasmid. Plasmids are then transformed into E.coli, one of the most cost-efficient and well-studied hosts. Too often these attempts to overexpress POIs in E.coli result in low yields or even no expression at all. To improve the production of challenging proteins-of-interest, we propose to use a collection of synthetic genes that encode de novo proteins as genetic fusion tags (DEEP-De novo Expression EnhancerProtein/s). These novel proteins are small (~100amino acids) and therefore do not impose a significant burden on the cell’s protein expression machinery. Moreover, they are highly stable, and easily purified without addition a supplemental affinity tag. Thus far, we have used this new method, to produce several biomedically important POIs in superior quantities relative to those fused to SUMO, a well-known and commercially available fusion tag of comparable size. In the current proposal, we would like to take advantage of the specific topology of DEEP to use it for the production of insulin. Initial results suggest that our novel technology for the production of insulin will result in: better yields of expression and purification, and faster and more efficient refolding. Together, these advantages will reduce the costs of insulin production, and lead towards a pharmaceutical therapy that is more available and more affordable to the expanding population of insulin users.