Molecular scaffolds for chemical wizardry: Learning nature's rules for terpene cyclases

Most people are familiar with terpenes whether they know it or not. These are the compounds that give many of our foods wonderful aromas and tastes and many of our household cleaning agents their fresh scents. But these are just some of the obvious ways we have taken advantage of these compounds. Biologically, terpenes are immensely important compounds in plants, fungi, bacteria, and insects that provide unique means for these organisms to sense and interact with their environment as well as serve as hormones that orchestrate developmental programs. For example, plants emit a wide range of terpenes that attract beneficial insects (1). Some plant families are notable also for their ability to synthesize and secrete antimicrobial terpenes as a defense compound against fungal and bacterial challenges (2). Still other plants that occupy resource-limited habitats such as deserts are known to constitutively secrete terpenes into their rhizosphere as a means of inhibiting the growth of competitor plant species (3). Fungi and bacteria likewise are known to synthesize a plethora of terpenes (4). Gibberella fujikuroi produces the well characterized plant growth regulator gibberellic acid, a diterpene, when it infects rice (5). This infection process results in unusually tall rice plants that can lodge easily and plants having other developmental abnormalities. Fusarium species and other relatives probably represent an even greater agricultural problem, because these fungi produce particularly noxious terpenes known as mycotoxins when they infect wheat and other stored grains (6).