Isotuberculosinol: the unusual case of an immunomodulatory diterpenoid from Mycobacterium tuberculosis

Abstract

Despite having served as a primary source for pharmaceutical agents, the physiological role played by natural products in their bacterial hosts is typically unknown. In addition, while terpenoids comprise the largest class of known natural products, it is unusual for these to be produced by bacteria. Accordingly, the recent findings demonstrating that Mycobacterium tuberculosis (Mtb) produces a diterpenoid, isotuberculosinol, is unusual in and of itself, and the accumulating evidence that this functions in the infection process of this pernicious human pathogen indicates a physiological role with medical relevance, all of which is reviewed here. Also presented is conservation of the biosynthetic capacity for isotuberculosinol production, which suggests that this is particularly important in Mtb, leading to speculation that this natural product may contribute to the highly infectious nature of Mtb in humans.