Recent advancements in soluble expression of recombinant antibody fragments in microbial host systems.

Recombinant fabs dominate the pharmaceutical pipelines today with microbial host systems continuing to be a major contributor toward their production. Escherichia coli is a versatile host for recombinant protein expression due to its simplicity, affordability, and ability to be cultivated at high cell density. It is particularly suitable for non-glycosylated proteins and small proteins. Despite the aforementioned benefits, the use of E. coli as the host for the synthesis of recombinant antibody fragments often suffers from low yield and reduced activity. In most cases, proteins are expressed as inclusion bodies and need to undergo refolding to achieve their active forms and this refolding step is generally low-yielding. In this article, we review the various approaches that researchers have taken to enhance the production of recombinant antibody fragments in E. coli. Molecular biology-oriented approaches such as cloning, chaperone-mediated folding, and host cell screening as well as process optimization involving examination of process parameters, media, and feeding have been addressed.