Browsing by Author "Morehouse, Nicholas J."

Now showing 1 - 6 of 6
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    Bioactive natural products from endophytic fungi
    (University of New Brunswick, 2019) Morehouse, Nicholas J.; Gray, Christopher
    Natural products are a source of diverse chemical structures with a broad range of bioactivities that provide valuable lead-compounds for drug development. This thesis explores the diversity of natural products biosynthesised by endophytes of marine macroalgae and medicinal plants. Fermentation extracts obtained from four endophytic fungi exhibited significant antimicrobial activity in our bioassay screens and their natural products chemistry was therefore investigated. This resulted in the isolation of poly(3R,5R-dihydroxyhexanoic acid), neobulgarones D, E and F, altenusin, (Z)-6R*,7S*- dihydroxy-2-propyl-2,4-octadien-4-olide, (Z)-6R*,7R*-dihydroxy-2-propyl-2,4-octadien4-olide and punctaporonins A, B, C, T and U. Of these natural products, six were found to possess antimicrobial activity and three were new chemical structures. The discovery of these new bioactivities and new chemical structures adds to the growing evidence that endophytic fungi are a source of chemical diversity and biologically relevant molecules.
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    Caryophyllene sesquiterpenes from a Chaetomium globosum endophyte of the Canadian Medicinal plant Empetrum nigrum
    (American Chemical Society, 2023-06-02) Morehouse, Nicholas J.; Clark, Trevor N.; Kerr, Russell G.; Johnson, John A.; Gray, Christopher A.
    Punctaporonins T (1) and U (2), new caryophyllene sesquiterpenes, were isolated with three known punctaporonins, A (3), B (4), and C (5), from the endophytic fungus Chaetomium globosum (TC2-041). The structures and relative configurations of punctaporonins T and U were elucidated based on a combination of HRESIMS, 1D/2D NMR spectroscopic analysis, and X-ray diffraction analysis whilst their absolute configuration is presumed to be consistent with the co-isolated 3–5 on biogenetic arguments. Compound 1 showed weak inhibitory activity against both Mycobacterium tuberculosis and Staphylococcus aureus.
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    Confirmation of the absolute stereochemistry of a polymeric natural product from a macroalgal endophyte
    (University of New Brunswick, 2018) Morehouse, Nicholas J.; Gray, Christopher; Johnson, John
    The bioactive biopolymer, poly(3,5-dihydroxyhexanoic acid), was previously isolated from an unidentified fungal endophyte of the marine macroalga Scytosiphon lamentaria. Literature reports for this compound failed to provide adequate details about poly(3,5-dihydroxyhexanoic acid) to allow for its complete characterization, thus requiring additional methods to be employed to determine the absolute stereochemistry of poly(3,5-dihydroxyhexanoic acid). Saponification of poly(3,5-dihydroxyhexanoic acid) yielded the lactone, 4-hydroxy-6-methyltetrahydro-2H-pyran-2-one. Nuclear magnetic resonance spectroscopy and polarimetry confirmed that the lactone was the 3R, 5R enantiomer, thus, the biopolymer isolated was confirmed to be poly(3R,5R-dihydroxyhexanoic acid).
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    Discovery of natural products from marine derived fungi and endophytic fungi
    (University of New Brunswick, 2023-10) Morehouse, Nicholas J.; Gray, Christopher A.
    Natural products are an abundant source of bioactive, complex, and diverse chemical structures. This thesis describes the isolation and structure elucidation of natural products biosynthesized by marine-derived fungi and endophytic fungi with the primary objective of the research being the discovery of new chemical structures. The thesis is divided into two parts: the discovery of new natural products and the development of a new dereplication platform. Three fungal isolates were investigated to discover new natural products. First, investigation of a Penicillium sp. fungus isolated from sea foam resulted in the discovery of a new phenalenone derivative that selectively inhibits the growth of Staphylococcus aureus and Mycobacterium tuberculosis. Second, investigation of an Aureobasidium pullulans fungus isolated from needles of Thuja occidentalis (white cedar), led to the isolation of two new C11-polyketides that inhibit the growth of Mycobacterium tuberculosis. Finally, investigation of a Tolypocladium sp. fungus isolated from the marine macroalga Spongomorpha arcta led to the isolation of two new lipopeptaibols that inhibit the growth of Gram-positive bacteria and mycobacteria. Although these five natural products are new, they are structural derivatives of previously discovered molecules rather than being structurally novel. To improve the likelihood of discovering novel natural products in the future, Structural similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS) was developed. SNAP-MS utilizes molecular networking topology and structural similarity fingerprinting to generate annotations of natural product compound families to aid in the dereplication process. This platform addresses limitations of many currently existing tools, such as the lack of publicly available reference data for most natural products and provides a new tool for analyzing complex mass spectrometry experiments that will improve dereplication capabilities and improve the likelihood of discovering novel natural products.
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    Isolation of an antimicrobial racemic phenalenone derivative from a marine-derived Penicillium sp. fungus
    (Canadian Science Publishing, 2023-10-30) Morehouse, Nicholas J.; Graham, Kelsie M.; Cox, Samantha L.; Johnson, John A.; Gray, Christopher A.
    A new phenalenone derivative, 2,4,6,9-tetrahydroxy-7-methyl-2-prenyl-1H-phenalene 1,3(2H)-dione (1), was isolated from the ethyl acetate extract of a marine derived Penicillium sp. fungus that exhibited a unique antimicrobial activity profile. The planar structure of 1 was determined through a combination of 1D and 2D NMR experiments, and circular dichroism and polarimetry indicated that it was isolated as a racemic mixture of enantiomers. The antimicrobial activity of 1 was assessed against a panel of Gram-positive and Gram-negative bacteria and fungal strains and it was found to selectively inhibit the growth of Staphylococcus aureus and Mycobacterium tuberculosis. Keywords: Phenalenone, Penicillium, Natural product, Antimicrobial
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    Tolypocaibols: Antibacterial lipopeptaibols from a Tolypocladium sp. endophyte of the marine macroalga Spongomorpha arcta
    (American Chemical Society, 2023-06-14) Morehouse, Nicholas J.; Flewelling, Andrew J.; Liu, Dennis Y.; Cavanagh, Hannah; Linington, Roger G.; Johnson, John A.; Gray, Christopher A.
    Two new lipopeptaibols, tolypocaibols A (1) and B (2), and the mixed NRPS-polyketide shikimate natural product maximiscin [(P/M)-3)] were isolated from a Tolypocladium sp. fungal endophyte of the marine alga Spongomorpha arcta. Analysis of NMR and mass spectrometry data revealed the amino acid sequences of the lipopeptaibols, which both comprise 11 residues with a valinol C-terminus and a decanoyl acyl chain at the N-terminus. The configuration of the amino acids was determined by Marfey’s analysis. Tolypocaibols A (1) and B (2) showed moderate, selective inhibition against Gram-positive and acid-fast strains, while maximiscin [(P/M)-3)] showed moderate, broad-spectrum inhibition.