Two rings in them all: The labdane-related diterpenoids

Unlike the majority of terpenoids, a significant fraction of the polycyclic diterpenoids (similar to 7000 already known) are now understood to originate from dual, rather than single, biosynthetic cyclization and/or rearrangement reactions, which proceed via a bicyclic diphosphate intermediate. The trivial name for the hydrocarbon skeleton of the most commonly found version of this biosynthetic intermediate forms the basis for a unifying labdane-related designation for this large super-family of natural products. Notably, many of these are found in plants, where the requisite biosynthetic machinery for gibberellin phytohormones, particularly the relevant diterpene cyclases, provides a biosynthetic reservoir that appears to have been repeatedly drawn upon to evolve new labdane-related diterpenoids. The potent biological activity of the ancestral gibberellins, which has led to the independent evolution of distinct gibberellin biosynthetic pathways in plants, fungi, and bacteria, is further discussed as an archetypical example of the selective pressure driving evolution of the large super-family of labdane-related diterpenoid natural products, with the observed diversification suggesting that their underlying hydrocarbon skeletal structures might serve as privileged scaffolds from which biological activity is readily derived.