Bottlenecks in the expression and secretion of heterologous proteins in Bacillus subtilis

Bacillus subtilis is an alternative host for expression and secretion of heterologous proteins. However, low yields of protein production limit its use on a wide scale. The secretory pathway of proteins can be divided into three functional stages: the early stage, involving the synthesis of secretory pre-proteins, their interaction with chaperones and binding to the secretory translocase; the second stage, translocation across the cytoplasmic membrane; and the last stage, including removal of the signal peptide, protein refolding and passage through the cell wall. Five bottlenecks for expression and secretion of heterologous proteins are described in this review: transcription, protein folding, translocation, signal peptide processing and proteolysis.