Tuesday, 31 January 2017

Preserving endangered trees, one phytochemical at a time.

Valuable phytochemicals give rise to plant poaching - Phytochemicals, chemicals produced by plants, have important roles in our economy, human health, and large scale ecosystems. Previous posts on this blog contain numerous interesting and hopefully entertaining examples. Over 30,000 species are used by humans for all sorts of things from fuels, to textiles, to food [1]. Lots of these plants have high monetary value, especially those that produce hard-to-find medicines or particularly complex molecules. Since they are worth quite a bit, such species are harvested from the wild, sometimes on large scales. Harvesting phytochemicals from wild plants that are extremely widespread or fast growing is often not a problem. However, harvest is a problem for species that are slow growing, or only grow in certain regions. Tree species are especially susceptible since they are slow growing and are often harvested faster than they can regenerate. As world population increases, how can we reconcile our increasing need for valuable phytochemicals with dwindling forest sizes?

Figure 1: Sandalwood scent molecules. Sandalwood, a popular incense and essential oil, comes from an endangered tree. Four chemical compounds, shown in white, comprise the sandalwood aroma. Genes encoding the molecular machinery that create these molecules were identified in Santalum album and have been transferred to yeast. Now it is possible to obtain these scent molecules without harming tree populations.

Valuable plant-derived scent molecules can be produced industrially after plant genome analysis - Fortunately, plant scientists and engineers are working together to solve this problem. For example, many native populations of the sandalwood tree, a popular source of scent molecules, are becoming endangered in certain areas due to over-harvesting [2]. In response, researchers at the University of British Columbia performed detailed analyses of sandalwood extract and found a family of molecules called santalols (lol) that are responsible for the sandalwood fragrance (Figure 1) [3]. Next, they performed detailed genetic analyses of several sandalwood trees and identified genes that are capable of producing the santalol molecule. Finally, they transferred these genes into a yeast culture, and after growing the yeast for several days, were able to extract the santalol molecules from the yeast. This research has laid the groundwork for a system in which the sandalwood scent could be produced from yeast cultures instead of harvesting it from endangered sandalwood trees, leaving the trees to thrive and contribute to their natural ecosystems.

Plant genome analysis enables acquisition of plant-derived medicines from crop species instead of endangered, wild species - Phytochemicals from slow-growing plants are also important medicines and therapeutics. The mayapple, also called the American mandrake(!), produces a compound called podophyllotoxin. By harvesting the mayapple, podophyllotoxin can be extracted and converted into another chemical called etoposide that kills dozens of types of malignant cancers (Figure 2). For this reason, the mayapple is harvested extensively and is now endangered in the eastern half of North America [4]. Chemical engineers at Stanford University carefully analyzed the mayapple's genome and found the six genes that create podophyllotoxin. They transferred these genes into tobacco plants, which are easy to grow, and these plants can now produce podophyllotoxin. In the future it will be possible to obtain podophyllotoxin by harvesting these modified tobacco plants instead of wild mayapple. Tobacco-derived podophyllotoxin can then be used to produce the cancer drug etoposide, likely lending an ironic twist to the history of the tobacco industry and cancer in humans.

Figure 2: Obtaining anti-cancer-etoposide from the mayapple. The mayapple can be harvested and extracted to obtain podophyllotoxin. While this compound has some medicinal properties, it can be converted into a potent chemotherapeutic called etoposide via chemical synthesis (that is, using chemical reactions in a chemistry lab). After genome analysis and molecular biology experiments, scientists have found how to create podophyllotoxin in tobacco plants, instead of harvesting mayapples from the wild.

Plant science for the environment! For biodiversity! - These two examples highlight the potential of genetic techniques to lessen our impact on our environment while increasing access to economically important and health-related chemical compounds. These examples also draw attention to the importance of publically-funded plant research programs; these programs stimulate industry, create new markets, and advance biotechnology. With more than 2,000 new species being discovered each year [1], who knows what plant scientists will discover next!

[1] Anderson, Seona, et al. "State of the world's plants - 2016." (2016).
[2] Arun Kumar, A.N., Joshi, G. and Mohan Ram, H.Y. (2012) Sandalwood: history, uses, present status and the future. Curr. Sci. 103, 1408–1416.
[3] Celedon, Jose M., et al. "Heartwood‐specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)‐santalol fragrance biosynthesis." The Plant Journal (2016).
[4] USDA Natural Resources Conservation Service https://plants.usda.gov/core/profile?symbol=POPE
[5] Warren Lau, and Elizabeth S. Sattely. "Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone." Science 349.6253 (2015): 1224-1228.