Optimization of Protein Secretion by Bacillus subtilis

The gram-positive bacterium Bacillus subtilis is widely known for its capacity to produce and secrete large amounts of industrially relevant proteins, mostly endogenous enzymes like proteases and lipases. The use of B. subtilis has many advantages, such as its GRAS status and the easy and inexpensive culturing methods that can result in very high cell densities. Over the years many patents have been filed regarding the optimization of protein secretion by B. subtilis. For almost every step in the production and secretion process, from promoter optimization to deletion of extracellular proteases, patents have been claimed. An overview of the current literature and patents on these subjects is given. We will discuss recent patents regarding the optimization of protein overexpression and secretion in B. subtilis. A patent claiming modification of B. subtilis SecA will be discussed in more detail. Another recent patent claims a positive effect of heterologous protein secretion upon reduced expression of the yusZ and/or yusX genes, encoding putative oligopeptidases. Improvements are being made continuously, although many depend on the character of the specific protein under study. Keywords: Bacillus subtilis, secretion, heterologous proteins, protein production, SecA, extracellular proteases, patents