A comparative analysis of signal peptide signatures in the bacterial cell factories Bacillus subtilis and Lactococcus lactis

Secreted recombinant proteins are of great significance for industry, healthcare and a sustainable bio-based economy. Due to their relatively simple cell envelope structure and effective protein secretion machinery, monoderm Gram-positive bacteria, such as Bacillus subtilis and Lactococcus lactis, are attractive cell factories for the secretory production of recombinant proteins of interest. Equally important for recombinant protein production as the secretion machinery are effective secretion signals, which direct proteins from the cytoplasm across the cytoplasmic membrane and cell wall into the fermentation broth. This notion called for a comparative analysis of the protein sorting and secretion signals that are operational in B. subtilis and L. lactis. Here, we present our comparative proteome-wide analysis of the species-specific signals that direct proteins into the respective secretory pathways and that may either lead to protein retention in the bacterial cells or secretion into the extracellular milieu. Furthermore, we compare proteome-wide identified signal peptides to those signal peptides that are actually used for recombinant protein production, thereby revealing remarkable differences in signal peptide lengths. Altogether, we anticipate that our present findings can serve as effective leads for the development of optimized signal peptides for secretory recombinant protein production in B. subtilis and L. lactis.