In order to fully exploit plant natural products we need to understand their biosynthesis. Eva Knoch's research project focuses on gene discovery in plant natural product biosynthesis in order to understand the production and roles of these compounds in plants. By PhD Eva Knoch, Center for Sustainable Resource Science Plants are outstanding chemists that produce a variety of natural products involved in their growth and development, and which help them deal with environmental stresses, pathogens, and herbivores. These natural products are also very interesting for humans, for example as pharmaceuticals. However, in order to fully exploit plant natural products we need to understand their biosynthesis. My research project focuses on gene discovery in plant natural product biosynthesis in order to understand the production and roles of these compounds in plants. This knowledge will contribute to the development of plants that adapt to future climate conditions and environmental challenges, and secure future food supply. In addition, biosynthetic enzymes identified have value as part of the synthetic biology toolbox and are useful for the development of novel natural products with pharmaceutical potential. Plants Are Outstanding Chemists Plants produce a wide range of complex molecules, also known as secondary metabolites or natural products. These chemicals play several roles in the plant (figure1). Natural products play important roles in the plant’s adaptation to the environment. They act as defence compounds against herbivores and pathogens, and are related to various stress responses. Natural products are therefore crucial to the plants’ ability to adapt to future climate conditions and environmental challenges. Figure 1. Plants are sessile organisms and have to deal with whatever the environment they took root in exposes them to. To cope with these challenges plants developed a wide range of chemicals that help them deal with environmental stresses, attack from pathogens and herbivores, to attract beneficial organisms, and even to communicate with other plants. Natural Products for Human Benefits The natural products produced by plants are also used extensively by humans for our own benefit. Since the very beginning, humans used plant natural products for medicines, spices, dyes, and recreational drugs1–3. Prominent examples of plant-derived medicines are morphine and codeine, caffeine, the anti-malaria compounds quinine and artemisinin (for the discovery of which Youyou Tu was awarded the Nobel prize in 20154), and the anti-cancer drug taxol (figure 2). Figure 2. Examples of plant derived natural products. Biosynthesis of Plant Natural Products The biosynthesis of natural products is catalysed by a number of specialised enzymes from different protein families. My research focuses on these biosynthetic enzymes of plant natural products, identifying biosynthetic pathways of natural products in order to fully investigate their functions in plants. Since natural products play important roles in relation to environmental challenges, understanding them fully is crucial to develop plants that can withstand the future environments brought on by global warming and continue to feed the growing global population. In that regard, this project contributes to meet the European Commission’s 21st Century Grand Challenges, which include food security. Another challenge is human health and the aging population, and also here can plant natural products contribute to solve the problems. Knowledge of the biosynthetic genes allows us to control the production of natural products in plants or to transfer the production of interesting compounds to production organisms such as yeast or microalgae5. While plants produce these highly complex chemicals, they often do not produce them in very high quantities. Extraction from natural sources is thus not always economically and environmentally sustainable. In addition, producing these compounds by means of chemical synthesis is often not feasible because of their complex stereochemistry. Thus, as the world’s population grows and ages, synthetic biology; using the biosynthetic enzymes to produce the compounds is the solution to sustainably and effectively supply the active agents of future medicines. Studying Plant Metabolomics and Hunting for Enzymes The field of plant natural products is very complex because many different chemicals coexist in the same plant and their analysis can thus be challenging. My host group under leadership of Professor Kazuki Saito at the Center for Sustainable Resource Science at RIKEN in Yokohama, Japan are world-leading in large-scale analysis of plant chemicals (a discipline known as metabolomics). The group has state-of-the-art instruments to measure a diverse spectrum of plant chemicals with high sensitivity. The grant from the Carlsberg foundation has enabled me to join this research group and train using these advanced instruments and learn metabolomics research methods from my skilled colleagues. These new tools will benefit my further career in plant natural product research, as they provide an important base for my future research. The extended, international network of scientist working at the frontier of plant metabolism that I have gotten thanks to my research stay in Japan is a source of inspiration and support for me. Model plants like Arabidopsis thaliana are very useful tools in many aspects of plant biology, as the entire genome is sequenced and many tools are available for this organism. However, the plants that produce interesting natural products are often not so well characterised. Identifying genes in interesting medicinal plants is more complicated, as no genome information for the plants exist. My host group successfully use their metabolomics approach integrated with transcriptomics (the study of active genes) to identify new pathways for natural product formation. I am very happy to be part of this team now and apply these approaches to find new enzymes for plant product biosynthesis. As an example of my research, I recently characterised an enzyme involved in the biosynthesis of a pollen specific natural product in petunia flowers. This compound is required during fertilisation and together with my colleagues I am currently investigating what role this enzyme plays in the fertilisation process. We are interested in this process as it may have direct impact on fruit and seed yield of crop plants. References 1. Cragg, G. M. & Newman, D. J. Natural Products: A continuing source of novel drug leads. Biochim. Biophys. Acta 1830, 3670–3695 (2013). 2. Atanasov, A. G. et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. (2015). doi:10.1016/j.biotechadv.2015.08.001 3. McChesney, J. D., Venkataraman, S. K. & Henri, J. T. Plant natural products: Back to the future or into extinction? Phytochemistry 68, 2015–2022 (2007). 4. Shen, B. A New Golden Age of Natural Products Drug Discovery. Cell 163, 1297–1300 (2015). 5. Møller, B. L. & Ratcliffe, R. G. Editorial overview: Synthetic plant biology: The roots of a bio-based society. Curr. Opin. Biotechnol. 26, ix–xvi (2014).