Research in the Peters laboratory is focused on the large class of diterpenoid natural products, largely those falling within the labdane-related superfamily. Bioactivity of these ~7,000 known compounds ranges from the gibberellic acid (GA) hormones ubiquitously found in higher/flowering plants to natural antibiotics, and includes compounds of pharmaceutical and industrial relevance. Their biosynthesis is unified in being initiated by a pair of terpene synthase catalyzed reactions. Beginning with a poorly understood acid/base catalyzed (class II) cyclization reaction, which forms the bicyclic core that defines this super- family of compounds, and proceeding through a more typical allylic diphosphate ionization driven (class I) reaction. The resulting cyclic hydrocarbon is generally then oxygenated via the action of cytochromes P450, with the ensuing compounds often further elaborated by redox reactions and/or addition of various chemical groups by transferases.
The importance of GA for plant growth and development resulted in early investigations of their biosynthesis including identification of all the enzymes involved in GA metabolism from plants, as well as from the phytopathogenic fungus Gibberella fujikuroi, from which GA was first isolated. We are engaged in mechanistic studies of the relevant enzymes from the model plant species Arabidopsis thaliana. This provides deeper insights into this critical metabolic pathway, e.g. for identification of potential biochemical regulatory mechanisms, and also provides a baseline against which the specificity of enzymes involved in alternative biosynthetic pathways can be measured. In addition, we have begun investigating the production of GA by certain (rhizo)bacteria as well.