Cyclitols and Aminocyclitols as Signals: Their Roles in Supporting Ecosystems and Promoting Human Health

Secondary metabolites (a.k.a. natural products) are believed to play beneficial roles for the producing organisms, such as coping with environmental stress or outcompeting other organisms. Some of them may function as signals. One such class of natural products is the cyclitol/aminocyclitol family of compounds, which includes myo-inositol and its derivatives, the aminoglycoside antibiotics, and the C7-cyclitols and C7N-aminocyclitols. While the function of inositol and its derivatives as intracellular signaling molecules has been well established, more recent studies have also demonstrated their important ecological roles. Studies have also shown that aminoglycoside antibiotics may function as signals that regulate biofilm formation in bacteria and secondary metabolite production in fungi. Several C7-cyclitols and C7N-aminocyclitols, e.g., acarbose, validamycin, and kirkamide, have been associated with gut microbiota modulation, gene regulation in fungi and insects, and/or plant-bacteria endosymbiosis. While mycosporine-like amino acids (MAAs) are well known for their UV-protective activities, studies with human cells and animals have shown intriguing biological activities involving gene regulation and activation of signaling pathways. This article reviews the roles of this family of natural products as signaling molecules involved in various biological events, including bacterial colonization and gene regulation, with physiological and ecological implications that may affect human health and other organisms.