The problem of expression of multidisulfide bonded recombinant proteins in E. coli

Abstract

Recombinant proteins currently play an important role in the pharmaceutical industry. Very frequently, proteins of therapeutic value contain complex disulfide bond patterns that are necessary for folding, stability, and/or function. Although the folding of proteins with multiple disulfide bonds in E. coli poses considerable challenges, a number of approaches developed in recent years can now be deployed for the production of such proteins at significant yields. Here, we present a summary of disulfide bond formation in E. coli and the main strategies aimed toward optimization of multidisulfided recombinant protein expression by secretion into the periplasmic space, expression in the cytoplasm of strains engineered to favor the formation of disulfide bonds in that compartment, and finally cell-free synthesis. © 2011 Springer Science+Business Media, LLC.