1. The biosynthesis of natural products (genome mining, engineered biosynthesis)
2. The enzyme biocatalysts (structure-based engineering, mechanistic studies)
3. The search for bioactive substances (isolation, structure elucidation, synthesis)
The main focus of our research has been to understand the mechanism of formation of a wide variety of naturally occurring substances. A multidisciplinary approach involving synthesis, enzymology, molecular biology, and structural biology is employed to address fundamental problems at the interface of chemistry and biology.
Natural organic compounds, prominent among which are antibiotics such as penicillin, are gifts from nature, and the benefits they have bestowed upon humankind as sources for the pharmaceuticals, etc., that maintain health is inestimable. The natural products chemistry is a domain of scholarship that creates a comprehensive science at the levels of the substance, enzymes, and genes to search for natural organic compounds, determine their structure, explore their bioactivity, and elucidate the mechanism of their biosynthesis. In our laboratory, we study the process of biosynthesis of natural organic compounds produced by plants and microorganisms, using not only the foundation discipline of organic chemistry, but also incorporating the methods of biochemistry and molecular biology in an effort to understand the enzymes that catalyze each biosynthesis reaction and the functions and control mechanisms of the genes that govern their expression at the molecular level. In addition, we are expanding our research into "engineered biosynthesis", by which rational systems for the biological production of new and useful substances can be designed and constructed, based on the mechanisms of biosynthesis that have been brought to light. Further, manipulation of the enzymes responsible for generating the core skeletons of pharmaceutically important secondary metabolites (e.g. polyketides and isoprenoids) leads to production of biologically active "supra-natural" products with remarkable structural diversity. We also are carrying out research on the mechanisms by which the bioactivity of natural products is expressed, while at the same time searching for natural products that are active in intracellular signaling. Developing effective strategies to discover and exploit new small molecules is integral to the success of future drug discovery efforts.