Secretory Production of Therapeutic Proteins in Escherichia coli.

Escherichia coli has been the workhorse for the production of recombinant proteins (1,2). However, problems often occur in recovering substantial yields of correctly folded proteins. E. coli cannot produce some proteins containing complex disulfide bonds or mammalian proteins that require posttranslational modification for activity. Overexpressed proteins are often produced in the form of inclusion bodies, from which biologically active proteins can only be recovered by complicated and costly denaturation and refolding processes. Various techniques have been developed to solve these problems, including the use of different promoters to regulate the level of expression, using different host strains, coexpression of chaperones, reduction of culture temperature, and secretion of proteins into the periplasmic space (see Fig. 1). Fig. 1.Strategies for the production of recombinant proteins in E. coli. Arrow A can be achieved by one of the methods described for the conversion of "Not secreted" to "Efficient secretion." [ABSTRACT FROM AUTHOR]