Cyclic di-adenosine monophosphate as a potential regulator of sporulation and solventogenesis in Clostridium beijerinckii: a hypothesis.

Cyclic di-adenosine monophosphate (c-di-AMP) is a versatile bacterial signaling molecule involved in the regulation of cell wall metabolism, response to osmotic stress, growth, maintenance of DNA integrity, potassium homeostasis, and sporulation. Recent studies have implicated c-di-AMP in the regulation of sporulation and solventogenesis in Clostridium beijerinckii, a model solventogenic Clostridium species (SCS). In light of emerging findings, in this review, we hypothesize that c-di-AMP plays a central role in regulating solventogenesis and sporulation in C. beijerinckii, a mechanism that may also occur in some other SCS. In SCS, sporulation and solventogenesis are strongly linked, with spore formation advancing proportionally to increasing butanol concentration. Given the membrane damaging effect of butanol on vegetative cells, spore formation allows SCS to package their DNA in a robust endospore that is resistant to numerous stressors. This ensures the propagation of future generations. c-di-AMP functions as a checkpoint in spore formation and repair of DNA damage-which guarantees the assembly of wholesome DNA during sporulation-as well participating in the regulation of cell wall metabolism and membrane-damaging osmotic stress, which may mimic butanol-mediated membrane damage. These suggest that c-di-AMP may serve as a regulatory anchor that operates at the nexus between maintenance of DNA integrity, sporulation, response to osmotic stress, and ultimately, butanol biosynthesis. In this review, we explore the potential role of c-di-AMP as a regulator of sporulation and ultimately, in C. beijerinckii as a model SCS.