Post-translational secretion stress regulation in Bacillus subtilis is controlled by intra- and extracellular proteases

N Biotechnol. 2023 Dec 27;79:71-81. doi: 10.1016/j.nbt.2023.12.009. Online ahead of print.ABSTRACTThe Gram-positive bacterium Bacillus subtilis is a prolific producer of industrial enzymes that are effectively harvested from the fermentation broth. However, the high capacity of B. subtilis for protein secretion has so far not been exploited to the full due to particular bottlenecks, including product degradation by extracellular proteases and counterproductive secretion stress responses. To unlock the Bacillus secretion pathway for difficult-to-produce proteins, various cellular interventions have been explored, including genome engineering. Our previous research has shown a superior performance of genome-reduced B. subtilis strains in the production of staphylococcal antigens compared to the parental strain 168. This was attributed, at least in part, to redirected secretion stress responses, including the presentation of elevated levels of the quality control proteases HtrA and HtrB that also catalyse protein folding. Here we show that this relates to the elimination of two homologous serine proteases, namely the cytosolic protease AprX and the extracellular protease AprE. This unprecedented posttranslational regulation of secretion stress effectors, like HtrA and HtrB, by the concerted action of cytosolic and extracellular proteases has important implications for the biotechnological application of microbial cell factories. In B. subtilis, this conclusion is underscored by ...

Source: New Biotechnology - December 29, 2023 Category: Biotechnology Authors: Ay şegül Öktem Dicky A Pranoto Jan Maarten van Dijl Source Type: research