The biosynthesis of tetramic acids

这项建议概述了旨在详细检查天然产物大杀菌素A的生物合成的研究。大杀菌素A由植物定植真菌Phoma Macstoma产生，大杀菌素A属于一类重要的天然产物，称为四酸。由萨斯卡通加拿大农业和农业食品研究站的Karen Bailey博士领导的一个研究小组展示了对这种分子的兴趣，该小组选择性地在加拿大蓟等阔叶植物上定居，而小麦和大麦等禾本科植物不受影响。当用真菌处理时，阔叶草看起来漂白和发育不良，这给了未受影响的草一个竞争优势。看来，大杀菌素A对阔叶杂草的影响至少是部分原因。这项工作表明，大口青霉可能是一种对环境无害的传统化学除草剂的替代品。我们建议研究大口青霉中大杀菌素A的生物合成，并利用这一信息来研究这种化合物在作物保护中可能起到的作用。这些知识将形成基础，以研究参与大口青霉生物合成途径的单个酶，并确定每个酶在生产大杀菌素A中的作用。这个项目将对更广泛的天然产品化学家社区有理论上的兴趣，因为四酸是一类具有有趣的生物活性的分子。这项研究将有助于建立一个计划，该计划将配备检查其他四酸，并有助于推动寻找新的和有趣的生物活性分子来自自然。

This proposal outlines research aimed at examining in detail the biosynthesis of the natural product Macrocidin A. Produced by the plant colonizing fungus Phoma macrostoma, Macrocidin A belongs to an important group of natural products known as tetramic acids. Interest in this molecule is sparked by the fact the P. macrostoma fungus has been shown by a research group led by Dr. Karen Bailey at Agriculture and Agri-food Canada research station in Saskatoon to selectively colonize broadleaf plants such as Canada thistle while leaving grasses such as wheat and barley unaffected. The broadleaf weeds appear bleached and stunted when treated with the fungus giving the unaffected grasses a competitive advantage. It appears that Macrocidin A is at least partially responsible for the effect on the broadleaf weeds. This work suggests that P. macrostoma may represent an environmentally benign alternative to traditional chemical herbicides. We are proposing to examine the biosynthesis of Macrocidin A in P. macrostoma and use this information to examine what role this compound may have in crop protection. This knowledge will form the foundation to examine individual enzymes involved in the biosynthetic pathway in P. macrostoma and to determine the role of each in the production of Macrocidin A. This project will be of theoretical interest to the wider community of natural products chemists as tetramic acids are a class of molecules with an interesting array of bioactivity. This research will help establish a program that will be equipped to examine other tetramic acids, and help advance the search for new and interesting biologically active molecules derived from Nature.