Healing with medicinal plants is as old as humankind itself. Even today, some of the most extensively used drugs such as aspirin, morphine, and quinine are directly extracted from plants. Unlike synthetic drugs, plant natural products are evolutionarily pre-selected chemicals against a wide spectrum of pathogens and other stresses in the environment. However, most plant-based medicines, although biologically effective, have not entered the realm of modern medicine. The biggest challenge is the lack of effective and sustainable methods for producing plant-based medicines because they are present at extremely low concentrations, sometimes less than 0.0001% of fresh weight. The current strategy of farming host plants is unlikely to meet the increasing demand for plant-derived drugs. In addition, these natural products usually have complex chemical structures, and conventional drug synthesis has not been able to produce them in a cost-effective manner.
The long-term goal in my laboratory is to provide alternative solutions for the sustainable and economical production of plant-based medicines through metabolic engineering and synthetic biology. In particular, we build novel metabolic pathways and reroute native pathways in microorganisms such as E. coli and yeast for the production of plant-derived drugs. Our current focus is terpene, the largest family of plant natural products. Many essential medicines including anti-cancer drug paclitaxel, vinblastine, and vincristine, are terpenes or terpene derivatives. Moreover, a complete understanding of biosynthesis pathways in host plants precedes any engineering efforts for scalable production of plant-based medicines. To this end, we are investigating the missing genes in the biosynthesis of digoxin—an important medicine on the World Health Organization’s (WHO) list of essential medicines for the treatment of heart failure. With the unprecedented technological advancement including DNA synthesis, -omics tools, and genome editing in recent years, we hope to tap into the great diversity of plant natural products to benefit the human health."