Gram-Positive Bacteria as Host Cells for Heterologous Production of Biopharmaceuticals

Abstract

The increasing demand of recombinant compounds in bioscience and bioindustries requires the further exploration and improvement of production systems including bacteria, fungi, insect and human cells. For compounds that do not require glycosylation for biological activity, microbial systems are most favourable hosts because of high level expression and relatively inexpensive culture systems. Traditionally, Escherichia coli was and still is most often the host of choice. However, the major drawbacks of this Gram-negative organism are the periplasmic location of the secreted proteins of interest due to the presence of an outer membrane and the frequent occurrence of cytoplasmically or periplasmically located inclusion bodies consisting of denaturated recombinant proteins. Gram-positive bacteria secrete the protein of interest directly into the culture media, thereby greatly facilitating downstream processing and protein recovery. As a consequence, they are being extensively explored for recombinant protein production. This report reviews the possible applications of Gram-positive bacteria as host cells for the production of proteins of biopharmaceutical interest. It will also highlight eventual advantages of Gram-positive bacteria compared to Gram-negative organisms. Although successful in some cases, several bottlenecks in the secretion of heterologous proteins remain. Approaches undertaken to improve the yield of secreted recombinant proteins in these Gram-positive bacteria will be summarised. Finally, results obtained so far regarding the production of biopharmaceutical compounds in a soluble active form and with respect to the cell surface display of recombinant proteins by Gram-positive bacteria will be discussed. 277 A. Van Broekhoven et al. (eds.), Novel Frontiers in the Production of Compounds for Biomedical Use, 277-300.