Investigating unknown medicinal plant natural product biosynthetic mechanisms has long been an interest of our lab. Unlike natural product biosynthetic genes in microbes, which often form biosynthetic gene clusters, genes in plant specialized metabolic pathways are, more often than not, scatter across the genome. This makes gene discovery for plant natural product biosynthetic pathways particularly challenging. To overcome this difficulty, we leverage state-of-the-art metabolomics and genomics technologies, along with comprehensive computational approaches, to identify candidate genes involved in a metabolic trait of interest. These candidate genes are then functionally examined both in vitro and in vivo. This line of work not only advances our knowledge about unknown biochemical processes underlying natural product synthesis, but also serves as the prerequisite for devising metabolic engineering strategies to enable sustainable production of valuable plant compounds.
We select the biosynthetic systems to study based on several criteria: the clinical importance and therapeutic potential of the natural product, unique chemical moieties of the natural product suggesting unprecedented biochemistry, and the scarcity of the natural product via conventional plant extraction. Besides enzymes that make up the biosynthetic pathways, we also aim to understand the high-order organization of metabolism within the cell, by organellar compartmentalization and/or membraneless metabolon formation, which contribute to efficient and precise metabolic flux control in several documented plant specialized metabolic processes.