Difference between revisions of "Maeda Lab:Research"

Research Interests in Maeda Lab

As sessile organisms, plants produce a tremendous array of organic compounds using CO₂, underground nutrients, and sunlight energy to survive in challenging ecological niches. This plant chemical diversity is achieved by the diversification of plant metabolic pathways far beyond central metabolism. Although extensive efforts are currently being made to understand these plant-specific metabolic pathways, we still have a limited knowledge of how plants allocate available carbon, fixed by photosynthesis, to a variety of downstream metabolic pathways. This fundamental knowledge gap also creates a bottleneck in effective plant breeding and metabolic engineering for the improved production of targeted metabolites. To address this issue, we focuses on understanding the biosynthetic pathways and regulatory mechanisms of plant primary metabolism, specifically the shikimate and phenylalanine/tyrosine pathways, which allocate up to 30% of photosynthetically fixed carbon for the production of numerous plant natural products (e.g., lignin, flavonoids, antioxidants, alkaloids). Our research specifically focuses on the following two projects.

The tyrosine biosynthetic pathway in plants

• Tyrosine (Tyr) is an aromatic amino acid required for protein biosynthesis in all living cells and, due to the absence of Tyr biosynthesis in animals, is an essential nutrient in human diets. In plants, Tyr also serves as a precursor of numerous natural products, which include tocopherols (vitamin E), cyanogenic glycosides, suberin, and isoquinoline alkaloids (e.g., analgesic morphine and codeine). These Tyr-derived plant metabolites have a remarkable structural complexity and a variety of pharmacological and biological activities, making them effective nutritional compounds and pharmaceutical drugs. However, often the low yields of these compounds in plant tissues hamper their commercial production in plants and there is a growing need to rationally engineer the plant Tyr pathway.
• In this project, we use table beet (Beta vulgaris) as a model system, which produces high levels of Tyr-derived pigments, betalains. Using an integrated approach of genetics, biochemistry, and analytical chemistry, our research aims to define the biosynthetic route leading to Tyr formation in plants and understand its regulation. We will further engineer the pathway to improve the production of Tyr and betalains in table beets as a proof of concept, which can be applied to other plant species for enhanced production of Tyr-derived compounds with nutritional and medicinal values.

The regulation of the plant shikimate pathway

• The shikimate pathway provides chorismate, a common precursor of all three aromatic amino acids (phenylalanine, tyrosine, and tryptophan). In microbes, the first enzyme of the shipmate pathway, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS), is tightly regulated by aromatic amino acids and controls carbon flux through the shikimate pathway. In plants, previous biochemical studies showed that the plant DAHPS enymzes are not sensitive to aromatic amino acids, suggesting that plants have a different mechanism regulating the shikimate pathway. This notion is not surprising as aromatic amino acids are not the final products and further used to produce a number of downstream metabolites in plants. Currently, we have limited knowledge of the plant enzymes involved in the early steps of the shipmate pathway and the regulation of the shikimate pathway is poorly understood in plants.

• In this project, we apply a unique integrated approach of bioinformatics, enzymology, forward/reverse genetics, cell biology, and analytical chemistry including stable isotope-assisted metabolic flux analyses. Our research aims are to i) characterize enzymes involved in the early steps of the plant shipmate pathway, ii) explore cellular organization of the shikimate and tyrosine/phenylalanine pathway enzymes in plants, and iii) understand the regulation of carbon flux through the plant shipmate pathway.