CIME extra seminar: Bacillus protein secretion - known unknowns!

Bacillus subtilis is one of the most widely exploited industrial microorganisms, used for the production of a variety of industrial products including enzymes, vitamins, amino acids, antifungal and antibacterial peptides, and surface-active agents such as surfactin. Analysis of this bacterium over more than 60 years has revealed detailed knowledge of its biochemistry, physiology and genetics, making it one of the most amenable for use as a synthetic biology/industrial biotechnology chassis. B. subtilis efficiently secretes native proteins and those from related bacteria at concentrations in excess of 20 g/L. However, yields of foreign proteins, such as mammalian therapeutic proteins, is much more variable  (μ ­ mg/L). With a view to addressing the issue of why Bacillus species are generally poor secretors of foreign proteins, we have systematically identified, and attempted to overcame, various bottlenecks in the secretion pathway. In particular, we have attempted to identify the characteristics that distinguish native from foreign proteins. In part, the answer lies in the relationship between the rate of folding and structure of native secretory proteins and what we refer to as the cell’s Quality Control Machinery. The seminar will review our current understanding of the Bacillus protein secretion and identify stages in the pathway that are still poorly understood ­ the "known unknowns”.