Transport of proteins across biological membranes is a crucial process in all kingdoms of life. In bacteria, the transport of proteins out of the cytosol is mediated mainly by two mechanistically different export pathways the general secretion (Sec) pathway and the twin-arginine-translocation (Tat) pathway. Current research of our group focusses on the investigation of various mechanistic aspects of Sec- and Tat-dependent bacterial protein translocation, such as substrate-translocase interactions and maintenance of pathway specificity.
The secretory production of proteins possesses significant process advantages compared to their intracellular production. Due to the lack of an outer membrane, Gram-positive bacteria are considered especially interesting as host organisms for the secretory production of proteins. In fact, the enormous secretion potential of this class of microorganisms is one of the reasons for their extensive use in industry for the secretory production of homologous or closely related proteins. In contrast, attempts to use Gram-positive bacteria as host organisms for the secretory production of heterologous proteins (e.g. pharmaceutical proteins) frequently fail or lead to disappointing results. This is due to several bottlenecks in the secretion pathways which, alone or in combination, can dramatically decrease the amount of the desired product in the culture supernatant. Ongoing work in our group aims at a detailed understanding of these bottlenecks at a molecular level in different Gram-positive bacteria (Bacillus subtilis, Staphylococcus carnosus, Corynebacterium glutamicum) and the subsequent development of strategies for the selective improvement of Gram-positive bacteria as cell factories for the secretory production of biotechnological relevant heterologous proteins and peptides.