STRUCTURES OF LIGNAN AND ISOFLAVONOID REDUCTASES, SEARCHING FOR THEIR MOLECULAR

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 木质素、木脂素和木脂素是维管植物的主要成分，占生物圈中循环的有机碳的近30%。本研究项目的重点是三种酶，在木脂素和木脂素的生物合成中具有关键作用。木脂素和木聚糖在植物防御和通讯中起着重要作用，帮助宿主区分生物病原体和共生非病原体。 除了它们在植物中的生理作用之外，这些化合物还具有显著的抗微生物、抗真菌、抗病毒、抗氧化和抗癌特性。因此，木脂素和木脂素被用作药理学药物，特别是用于各种癌症的临床治疗。人们普遍认为，以植物为基础的饮食的人癌症发病率低是由于这些木脂素和木脂素的预防作用。出于这些原因，人们对通过定义和利用木脂素和异黄酮生物合成途径使这些化合物更普遍地可用产生了相当大的兴趣。这些方法由于缺乏有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而受到严重阻碍。本项目的目标是通过高分辨率的X射线结构来确定木脂素和木脂素生物合成中关键酶的结构-功能关系。这些研究结果对探索木脂素类化合物在植物生态保护中的调控作用，以及工业规模的区域特异性和立体特异性合成具有重要意义

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 synthesis