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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-E (40))
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Cornell University
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