STRUCTURES OF LIGNAN AND ISOFLAVONOID REDUCTASES, SEARCHING FOR THEIR MOLECULAR

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。木质素、木脂素和异黄酮类化合物是维管束植物的主要成分，占生物圈中循环的有机碳的近30%。本研究主要针对木脂素和异黄酮类化合物生物合成中的三种关键酶进行研究。木脂素和异黄酮类化合物在植物防御和交流中发挥着重要作用，帮助寄主区分生物病原菌和共生非病原菌。除了它们在植物中的生理作用外，这些化合物还具有显著的抗菌、抗真菌、抗病毒、抗氧化和抗癌特性。因此，异黄酮类和木脂素类化合物被用作药物，特别是用于各种癌症的临床治疗。人们普遍认为，植物性饮食的低癌症发病率是由于这些木脂素和异黄酮类化合物的预防作用。由于这些原因，人们对通过定义和开发木脂素和异黄酮类生物合成途径来使这些化合物更普遍地可用有相当大的兴趣。由于缺乏有关相关酶的详细信息，以及使用组织(或细胞)培养获得这些化合物的成功有限，这些方法受到严重阻碍。该项目的目标是通过高分辨率X射线结构确定木脂素和异黄酮类生物合成中关键酶的结构-功能关系。这些研究为探索木脂素和异黄酮类化合物在生态植物保护中的调控，以及工业化规模的区域特异性和立体特异性合成提供了有用的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lignins, lignans and isoflavonoids are major constituents of vascular plants and account for nearly 30% of the organic carbon circulating in the biosphere. This research project focuses on three enzymes that have critical roles in lignan and isoflavonoid biosynthesis. Lignans and isoflavonoids play important roles in plant defense and communication, helping hosts discriminate between biological pathogens and symbiotic non-pathogens. In addition to their physiological roles in plants, these compounds have pronounced antimicrobial, antifungal, antiviral, antioxidant and anticancer properties. Therefore, isoflavonoid and lignan are used as pharmacologicals, especially for the clinical treatment of various cancers. It is generally accepted that low cancer incidence in people with plant-based diets is due to the preventive effect of these lignans and isoflavonoids. For these reasons, there is considerable interest in making these compounds more generally available by defining and exploiting the lignan and isoflavonoid biosynthetic pathways. These approaches are seriously hampered by a lack of detailed information on the involving enzymes and by limited success in obtaining these compounds using tissue (or cell) culture. The goal of this project is to define the structure-function relationships of the critical enzymes in lignan and isoflavonoid biosynthesis through high-resolution x-ray structures. The information gained from these studies will be very useful for exploring the regulation of lignans and isoflavonoids for ecological plant protection, and industrial-scale regiospecific and stereospecific synthesi