Graduate Thesis Or Dissertation


Metabolomic Profiling of Natural Products from Two Tolypocladium Fungal Species as Part of An Evolutionary Genomics Study Public Deposited

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  • This thesis describes an investigation of the natural products chemistry of two fungal species of the genus Tolypocladium. Natural products are small organic molecules that are considered non-essential for cell growth and reproduction, and thus part of secondary metabolism. Chemical profiling of these secondary metabolites using a combination of high-performance liquid chromatography (HPLC) and mass spectrometry (MS), as well as ¹H nuclear magnetic resonance (NMR) spectroscopy, identified a number of known and unknown natural products of Tolypocladium inflatum and T. geodes. In particular, putative new peptaibols were detected by LC- MS MS profiling, although these data were insufficient for structural characterization. To determine the effect of a putative secondary metabolite regulator, comparative metabolomic profiling was performed of T. inflatum wild-type and a knockout mutant in which the genes for a homolog of the histone methyltransferase KMT6 had been deleted. A preliminary result on the deletion of the kmt6 gene homolog suggests a knockdown of CsA and possibly the putative new peptaibols. Finally, to demonstrate the potential of T. inflatum to produce medicinally-relevant molecules with new biological activities, extracts and fractions were screened against the human pathogen Neisseria gonorrhoeae. Some test samples appeared to possess potent activity and, suggesting that they contain compounds, which inhibit the growth of N. gonorrhoeae.
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