Discovering and Engineering of Plant Chemistry
for Plant and Human Health
In our lab we are fascinated by the ability of plants to make so many molecules critical to life, from food and medicine to materials and fuel. Given that plants all do this starting from the world’s simplest building block, CO2, fixed on the order of 5000 tons/sec, we think plants are the best chemists on the planet! For example, plants provide ~10% of clinically used therapeutics and are the backbone of our food supply. Despite the major impact of plants on human health and the environment, many of the ways we use plants are ripe for disruption: numerous drugs are still isolated from difficult-to-cultivate medicinal plants, the chemistry of dietary crops is poorly understood and unoptimized, and there are significant environmental and humanitarian challenges in our current agriculture systems. The merger of engineering and plant chemistry holds promise for a great leap forward in how we use plants; a major challenge is to identify the genes that make up plant metabolic pathways as the first step towards engineering new chemistry.
A central mission of our laboratory is to reveal how plants use their chemistry to grow into the largest and longest-living organisms on earth. Ultimately, we would like to be able to use this knowledge of plant pathways to engineer plant proteins and metabolites in a way that will make agriculture more sustainable and prevent human diseases caused by diet. Along the way, we hope our science will inspire the broader community to celebrate and preserve the valuable plant kingdom. Our lab is a collaborative, supportive, and inclusive community of scientists and engineers who strive to bring an interdisciplinary approach to important problems in plant chemistry. Trainees in the lab become experts in metabolism, genetic engineering, and synthetic biology.
Four areas of focus on the Sattely lab:
(1) Discovery and engineering of metabolic pathways for plant molecules. Many of these pathways can be directly used to produce important but difficult-to-access therapeutics from plants (e.g. taxol and clinical candidates such as limonoids). Here, our goal is to expand the toolkit of enzymes that can be used to access chemically complex and valuable plant molecules, and ultimately for the bioproduction of new medicines. While our current approach is centered on plant molecules with promise in the clinic, related metabolic pathways from plants could be also engineered for sustainable production of chemicals and renewable materials.. Key publications and projects:
- Lau, W. and Sattely, E. S. “Six genes that complete biosynthetic pathway to the etoposide aglycone in Mayapple” Science, Vol. 349, No. 6253, pp. 1224-1228, 2015.
- Nett, R. S., Dho, Y.; Low, Y-Y.; Sattely, E. S. “A metabolic regulon reveals early and late acting enzymes in neuroactive Lycopodium alkaloid biosynthesis” Proc. Nat. Acad. Sci. 2021 https://doi.org/10.1073/pnas.2102949118.
- Nett, R. S. & Lau, W.; Sattely, E. S. “Discovery and engineering of colchicine alkaloid biosynthesis” Nature, 2020 doi: 10.1038/s41586-020-2546-8.
- Jeon, J-E.* & Kim, J-G.*; Fischer, C. R.; Mehta, N.; Dufour-Schroif, C.; Wemmer, K.; Mudgett, M. B. & Sattely, E. S.“A pathogen-responsive gene cluster for the production of highly modified fatty acids in tomato” Cell 2020, doi: 10.1016/j.cell.2019.11.037. *these authors contributed equally
(2) Discovery and engineering of metabolic pathways for enhancing plant fitness. Plants thrive in the face of virtually every environmental stress: low nutrient input, pathogen attack, drought, and high salinity. However, agricultural crops have been bred for yield and food quality, and often lack fitness-promoting traits common in wild plants. As a result, farming these crops requires enormous energy inputs in the form of fertilizer and water, >20% of crops grown each year are lost to disease, and just 1/3 of the world’s land mass is considered arable. Among the many proposals for how to feed our growing population, there is broad agreement that improving plant fitness under non-ideal growth conditions is critical. The key to achieving this goal is to identify specific mechanisms that confer fitness and are practical engineering targets. Our approach is to focus on identifying metabolic pathways that enable plants to combat pathogens, acquire nutrients, or associate with beneficial microbes. The pathways are then the starting point for using metabolic engineering approaches to enhance plant fitness. Key publications:
- Voges, M. J. E. E. E.; Bai, Y.; Schulze-Lefert, P.; Sattely, E. S. “Plant-derived coumarins shape the composition of an Arabidopsis synthetic root microbiome” PNAS 2019, 116, 12558-12565.
- Holmes, E. C.* & Chen, Y-C*; Sattely, E. S.; Mudgett, M.B. “Conservation of N-hydroxy-pipecolic acid-mediated systemic acquired resistance in crop plants” Science Signaling 2019 doi: https://doi.org/10.1126/scisignal.aay3066. *these authors contributed equally
- Rajniak, J; Barco, B.; Clay, N. K.; Sattely, E. S. “A New Cyanogenic Metabolite in Arabidopsis Required for Inducible Pathogen Defense” Nature, Vol. 525, No. 7569, pp. 276-279, 2015.
- Rajniak, J.; Giehl, R. F.; Chang, E.; Murgia, I.; von Wiren, N.; Sattely, E. S. “Secretion of redox-active metabolites as a general strategy for iron acquisition in plants” Nature Chem. Biol. 2018, 14, 442-450.
- De La Peña, R. and Sattely, E. S. “Re-routing plant terpene biosynthesis enables momilactone pathway elucidation” Nat. Chem. Biol. 2020 doi: https://doi.org/10.1038/s41589-020-00669-3.
(3) Determine how food chemistry influences human health and contributes to the development of disease. Much of our current work is focused on determining which food molecules are host relevant, and how the gut microbiota gates host exposure. Here, our long term goal is to determine how diet can be used in the prevent human disease. We are currently most interested in food allergy, and anticipate our approach will be broadly relevant to other diseases influenced by diet including cardiovascular disease and cancer.
- Liou, C. S.*, Sirk, S. J.* & Diaz, C. A. C.*; Klein, A. P.; Fischer, C. R.; Higginbottom, Erez, A.; Donia, H.; S, K.; Sonnenburg, J. L.; Sattely, E. S. “A metabolic pathway for glucosinolate activation by the human gut symbiont Bacteroides thetaiotaomicron” Cell 2020 doi: 10.1016/j.cell.2020.01.023. *these authors contributed equally
(4) Develop new tools to study plant pathways and their biology. Develop new tools to study plant pathways and their biology. Here we are leveraging new ideas in synthetic biology to develop high-throughput and plant-agnostic approaches for single cell genetic screens, transcriptomics, and bacteria-mediated DNA delivery. We anticipate these tools will help us rapidly unravel gene function and biochemical pathways in plants, and help with precision engineering of crops.
- stay tuned for upcoming publications in this focus area!
For project details, please see Group Members page