Remodeling Cell Wall Rigidity to Reduce Cell Lysis and Increase the Yield of Heterologous Proteins.

has great potential as a host for heterologous protein production, but its severe autolytic behavior has precluded its industrial application to date. Because d,l-endopeptidase activity-guided cell wall rigidity is considered essential for autolysis resistance, we investigated the effects of d,l-endopeptidase genes , , , and play on the growth, lysis, and morphology remodeling of strain TCCC11018. Individual and combinatorial deletion of , , and enhanced the cell growth and delayed cell lysis. For the best mutant with the and double deletion, the viable cell number at 24 h increased by 11.90% and the cell wall thickness at 6 h increased by 25.87%. Transcriptomic and proteomic analyses indicated that the improvement was caused by enhanced peptidoglycan synthesis. With the and double deletion, the extracellular green fluorescent protein and phospholipase D expression levels increased by 113 and 55.89%, respectively. This work broadens our understanding of the relationship between d,l-endopeptidases and cell characteristics, which provides an effective strategy to improve the heterologous protein expression in -based cell factories.