Cell biology of plant natural products

我的长期研究目标是了解植物天然产物（次生代谢物）的生物合成、运输和储存。植物是我们在工业和健康相关应用中使用的大量化学品的重要资源。在世界卫生组织确定的252种基本药物中，超过11%来自高等植物；更多的是从天然前体获得的合成衍生物。许多工业应用依赖于植物衍生的油和蜡，如荷荷巴（Simmondsia chinensis）蜡酯，它被用作汽车变速箱等高压应用的润滑剂。与健康有关和具有重要经济意义的植物天然产物的生物合成是一个活跃的研究领域，但对生物合成的细胞方面知之甚少。通常，次生代谢物的积累位点与生物合成位点在物理上是分离的；这些化合物中有许多对细胞有毒，必须小心储存。了解天然产物的定位和转运将对植物次生代谢途径的生物工程至关重要。我正在研究两个模型系统：拟南芥（Arabidopsis thaliana）的蜡分泌和黄花蒿（Artemisia annua）的青蒿素生物合成和运输。蜡质角质层是保护植物免受病原体和干旱侵害的保护层；了解角质层对农业非常重要。黄花蒿是一种重要的抗疟疾药物青蒿素的来源，但是生产成本的上升使得发展中国家的许多人难以获得这种药物，而发展中国家最需要这种药物。为了理解这一点，我最初的研究重点将放在atp结合盒（ABC）转运体上，这些转运体已被证明在许多物种的许多不同次生代谢物的运输和封存中发挥关键作用。这些ABC转运体的特征将有助于生产害虫和/或抗旱作物；通过作物改良或生物工程应用提高青蒿素产量。此外，了解这些系统中的转运将为理解植物天然产物的细胞生物学提供线索。

The long-term goal of my research is to understand the biosynthesis, transport, and storage of plant natural products (secondary metabolites). Plants are an important resource for a vast array of chemicals that serve us in industrial and health-related applications. Over 11% of the 252 drugs identified as essential by the World Health Organization are from higher plants; more still are synthetic derivatives obtained from natural precursors. Many industrial applications rely on plant-derived oils and waxes, such as Jojoba (Simmondsia chinensis) wax esters which are used as a lubricant in high-pressure applications such as automobile transmissions. The biosynthesis of health-related and economically important plant natural products is an active area of research, however less is known about the cellular aspects of biosynthesis. Often, the site of accumulation of a secondary metabolite is physically separated from the site of biosynthesis; many of these compounds are toxic to the cell and must be carefully stored. An understanding of the localization and transport of natural products will be essential for bioengineering of secondary metabolic pathways in plants.  I am studying two model systems: wax secretion in Arabidopsis thaliana and artemisinin biosynthesis and transport in Artemisia annua.  The waxy cuticle is a protective layer protecting the plant from pathogens and drought; and understanding of the cuticle is very important for agriculture. Artemisia annua is the source of artemisinin, an important anti-malarial drug, but the rising cost of production is making this drug difficult to obtain for many in the developing world, where it is most needed.  Towards this understanding, the initial focus of my research will be on ATP-binding cassette (ABC) transporters, which have been shown to play a key role in the transport and sequestration of many different secondary metabolites in many species. Characterization of these ABC transporters will be useful for producing pest and/or drought-resistant crops; improving artemisinin production through crop improvement or bioengineering applications.  Moreover, understanding transport in these systems will provide clues to understanding the cell biology of plant natural products in general.