Protein Secretion Systems of Corynebacterium glutamicum

Abstract

Corynebacterium glutamicum exhibits numerous ideal intrinsic attributes as a protein factory, including particularly the secretion of a limited number and quantities of endogenous proteins, a very low level of extracellular protease activity, and the presence of two different native protein secretion mechanisms that have been demonstrated to drive the excretion of homologous and heterologous proteins (the general secretory pathway and the twin-arginine pathway). Moreover, it is capable of glycosylation, a property that opens the possibility to manufacture humanized proteins in addition to industrial enzymes. What is more, efficient signal peptides and prodomain regions have already been identified in this bacterium together with zymogen activation protocols. Similarly, surface expression was demonstrated by successfully decorating the surface of C. glutamicum with α-amylase. However, the technology of corynebacterial host vector systems for protein production is still emerging since only a limited number of proteins have been produced to this date with this organism. The construction in optimized strains of optimized secretion vectors that are stable and in high copy numbers and that combine a strong and controllable promoter with efficient translation stabilization region, secretion and maturation signals remains to be achieved. Likewise, the fundamental biology underlying protein secretion in Corynebacteria, and the definition of the capabilities of this novel protein secretion system and its limitations need to be defined further in order to bring to the biotechnological practitioner an additional technological option for industrial enzymes and pharmaceutical biologics manufacturing. Results attained to date, however, demonstrate the strong potential of Corynebacteria for protein manufacturing.