ANALYSIS OF A NEW NATURAL PRODUCT FROM THE FUNGUS METARHIZIUM ACRIDUM

绿僵菌新天然产物的分析

• 批准号: 8363572
• 负责人: Stuart Krasnoff
• 金额: $ 1.02万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363572
• 关键词: Agriculture; Anabolism; Arthropods; Biological; Biological Factors; Caliber; Carbon; Family; Funding; Grant; Hand; Harvest; Insecta; Length; Macrolides; Mass Spectrum Analysis; Methods; Molecular; Molecular Genetics; Molecular Weight; National Center for Research Resources; Organism; Phenylalanine; Principal Investigator; Reporting; Research; Research Infrastructure; Resources; Source; Specimen; Structure; United States National Institutes of Health; X-Ray Crystallography; chemical standard; cost; fungus; novel; pathogen; retinal rods; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Metarhizium acridum is a cosmopolitan fungal pathogen of insects and other arthropods that has been developed as a biological control agent for numerous agricultural pests. Our group studies the small molecule metabolites produced by this fungus. Recently we reported the serinocyclins, a novel family of nonribosomal cyclic heptapeptides. Microbeam X-ray crystallography afforded a crystal structure that was critical in solving the complete absolute configuration for the compound. We have now isolated another novel compound from M. acridum and have solved its planar structure by mass spectrometry and NMR. It is a macrolide with the molecular formula C37H55NO6, has a molecular weight of 609, and incorporates a single unit of phenylalanine into a 17-membered ring. The molecule has a total of nine chiral carbons. Establishing the absolute configuration at the alpha-carbon of the PHE unit will be routine. However, establishing the absolute configuration of the remaining eight stereogenic centers will be difficult using standard chemical methods. Therefore, we propose to use X-ray crystallography to obtain a structure that will provide the complete absolute configuration of the compound, which will be possible once the configuration of the Phe unit is determined and the structure can be handed accordingly. We have crystallized the primary component and have harvested several crystal specimens, which grew as rods 100-300 microns in length but only 50 microns in diameter. The crystals have good and bad regions and are fragile and difficult to manipulate without breaking. Therefore we anticipate the need to use microbeam. A complete structural characterization will support our studies of the molecular genetics of biosynthesis of the small molecule metabolites of Metarhizium and will be critical in determining the biological significance of this compound to the producing organism.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 metarhizium acridum是一种昆虫和其他节肢动物的国际化真菌病原体，已作为许多农业害虫的生物控制剂开发。 我们的小组研究了这种真菌产生的小分子代谢产物。最近，我们报道了Serinocyclins，这是一个新型的非透射式环状七肽家族。 Microbeam X射线晶体学提供了一种晶体结构，对于求解化合物的完整绝对构型至关重要。 现在，我们已经将另一种新型化合物与Acridum M.隔离，并通过质谱和NMR解决了其平面结构。 它是一种具有分子式C37H55NO6的大环内酯，其分子量为609，并将单个单位的苯丙氨酸单位掺入17元的环中。该分子总共有9种手性碳。 在PHE单元的α-碳中建立绝对配置将是常规的。 但是，使用标准化学方法，难以建立其余八个立体中心的绝对配置。因此，我们建议使用X射线晶体学以获得将提供该化合物的完整绝对配置的结构，一旦确定了PHE单元的配置，并且可以相应地交付结构。 我们已经结晶了主要成分，并收集了几个晶体样本，它们的长度为100-300微米，但直径仅为50微米。 晶体具有好的区域和坏区域，并且脆弱，难以操纵而不破裂。 因此，我们预计需要使用微束。 完整的结构表征将支持我们对元小分子代谢物生物合成分子遗传学的研究，对于确定这种化合物对生产生物的生物学意义至关重要。