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Research in my group is centered on studies of diterpenoids.  These form a large group of natural products, with over 12,000 already known.  Notably, many (although certainly not all) of these diterpenoids 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 such natural products, which we have termed 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, provides an archetypical example of the selective pressure driving evolution of the large super-family of labdane-related diterpenoid natural products (~7,000 already known).  The observed diversification suggests that the underlying hydrocarbon skeletal structures serve as privileged scaffolds from which biological activity is readily derived.  Our studies encompass both investigation of metabolic pathways/networks and the underlying enzymatic mechanisms, along with elucidation of the physiological function of these natural products.  The diterpene synthases/cyclases involved in production of the labdane-related diterpenoids are representative of those involved in biosynthesis of all major classes of terpenoids, providing wider significance to our work.  Our studies have led to several fundamental insights into the intriguing mechanisms of the complex reactions catalyzed by these fascinating enzymes, highlighted by the profound effect that can be exerted by single residue changes on enzymatic activity.  Our work entails use of a wide variety of approaches, ranging from generating from atomic level structrures by X-ray crystallography to investigation of plant-plant and plant-microbe interactions at a multi-organism level.

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