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DOI: 10.1055/s-0036-1596122
Discovery of novel antibiotics from fungal endophytes by comprehensive LC-MS based metabolomics
Publication History
Publication Date:
14 December 2016 (online)
Secondary metabolites produced by fungal endophytes of grasses and conifer trees have been shown to play an important role in defense of the host against insect and fungal diseases. The discovery of new bioactive compounds is of great interest as endophytes have proven to be an excellent source of diverse and potent biological agents. In this study, we applied a metabolomics based approach to the investigation of secondary metabolites from 188 fungal endophytes of grapevines, raspberry, blueberry and cranberry plants. Extracts were analyzed by comprehensive LC-MS based metabolomics and spectral libraries of deconvoluted MS and MS/MS spectra were compiled. Data were compared to our in-house library for matches and screened against AntiBase, The Dictionary of Natural Products and NORINE for rapid dereplication of known compounds. PCA and OPLS-DA analyses of the LC-MS datasets provided a number of unique outlier extracts as targets for new compound discovery. LC-SPE and semi-preparative HPLC were used to isolate these compounds, which were characterized by LC-MS, NMR and single crystal X-ray diffraction (XRD). To date this work has led to the discovery of over 30 new bioactive compounds, several having new scaffolds, and 35 previously reported compounds. We have demonstrated that fungal endophytes from Canadian fruit-bearing plants are an excellent source of novel, new and known fungal secondary metabolites with important bioactivity. All of the known compounds produced by these endophytes are biologically active and remarkably, many have been evaluated for their use as pharmaceuticals. The bioactivity of these compounds suggests that they play an important role in defense against diseases and pests, and may have potential use in agricultural crop protection or as medicinal agents.
We thank T. McDowell, M. Kelman and J. Dimmers (AAFC – London) and F. Fei and Dr. H.A. Jenkins (McMaster) for technical support. We thank The Center for Chemical Biology (CMCB) and the Biointerfaces Institute (BI) at McMaster University for access to instrumentation. A. Ibrahim is support by an Ontario Graduate Scholarship (OGS) Doctorial Research Award.
Keywords: metabolomics, fungal endophytes, bioactivity.
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No conflict of interest has been declared by the author(s).