Protein expression and refolding--a practical guide to getting the most out of inclusion bodies

The release of sequence data, particularly from a number of medically and biotechnologically important genomes, is increasing in an exponential fashion. In light of this, elucidating the structure and function of proteins, particularly in a "high throughput" manner, is an important quest. The production of recombinant proteins however is not always straightforward, with a number of proteins falling prey to low expression problems, a high susceptibility to proteolysis and the often despised production of inclusion bodies. Whilst expression as inclusion bodies can often be advantageous, their solubilization and renaturation is often a time consuming and empirical process. In this review, we aim to outline some of the more common approaches that have been applied to a variety of proteins and address issues associated with their handling.