Metabolomics-guided isolation of anti-trypanosomal metabolites from the endophytic fungus Lasiodiplodia theobromae

Nurkhalida Kamal, Christina V. Viegelmann, Carol J. Clements, RuAngelie Edrada-Ebel

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. The application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. In this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for the medium-scale fermentation of the endophyte Lasiodiplodia theobromae. The (1)H NMR comparison between the active versus inactive fractions identified several unique chemical fingerprints belonging to the active fractions. Furthermore, by integrating high-resolution-liquid chromatography mass spectrometry data with multivariate data analysis, such as orthogonal partial least squares-discriminant analysis (OPLS-DA) and the bioactivity results of the fractions of L. theobromae, the anti-trypanosomal agents were easily discerned. With available databases such as Antibase and Dictionary of Natural Products coupled to MZmine through in-house algorithms optimized in our laboratory, the predicted metabolites were readily identified prior to isolation. Fractionation was performed on the active fractions and three known compounds were isolated, namely, cladospirone B, desmethyl-lasiodiplodin, and R-(-)-mellein. Cladospirone B and desmethyl-lasiodiplodin were among the predicted compounds generated by the OPLS-DA S-plot, and these compounds exhibited good activity against Trypanosoma brucei brucei with minimum inhibitory concentrations of 17.8 µM and 22.5 µM, respectively.

LanguageEnglish
JournalPlanta Medica
Early online date19 Oct 2016
DOIs
Publication statusE-pub ahead of print - 19 Oct 2016

Fingerprint

Endophytes
Metabolomics
Liquid chromatography
Discriminant analysis
Metabolites
Fungi
Mass spectrometry
Nuclear magnetic resonance
Discriminant Analysis
Least-Squares Analysis
Liquid Chromatography
Mass Spectrometry
Fractionation
Glossaries
Bioactivity
Biological Products
Fermentation
Assays
Trypanosoma brucei brucei
Dermatoglyphics

Keywords

  • metabolomics
  • natural products research
  • endophytic fungi
  • Lasiodiplodia theobromae
  • fungal endophytes
  • anti-trypanosomal activity
  • partial least square-discriminant analysis
  • fractionation
  • chemometrics

Cite this

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title = "Metabolomics-guided isolation of anti-trypanosomal metabolites from the endophytic fungus Lasiodiplodia theobromae",
abstract = "Fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. The application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. In this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for the medium-scale fermentation of the endophyte Lasiodiplodia theobromae. The (1)H NMR comparison between the active versus inactive fractions identified several unique chemical fingerprints belonging to the active fractions. Furthermore, by integrating high-resolution-liquid chromatography mass spectrometry data with multivariate data analysis, such as orthogonal partial least squares-discriminant analysis (OPLS-DA) and the bioactivity results of the fractions of L. theobromae, the anti-trypanosomal agents were easily discerned. With available databases such as Antibase and Dictionary of Natural Products coupled to MZmine through in-house algorithms optimized in our laboratory, the predicted metabolites were readily identified prior to isolation. Fractionation was performed on the active fractions and three known compounds were isolated, namely, cladospirone B, desmethyl-lasiodiplodin, and R-(-)-mellein. Cladospirone B and desmethyl-lasiodiplodin were among the predicted compounds generated by the OPLS-DA S-plot, and these compounds exhibited good activity against Trypanosoma brucei brucei with minimum inhibitory concentrations of 17.8 µM and 22.5 µM, respectively.",
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Metabolomics-guided isolation of anti-trypanosomal metabolites from the endophytic fungus Lasiodiplodia theobromae. / Kamal, Nurkhalida; Viegelmann, Christina V.; Clements, Carol J.; Edrada-Ebel, RuAngelie.

In: Planta Medica, 19.10.2016.

Research output: Contribution to journalArticle

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T1 - Metabolomics-guided isolation of anti-trypanosomal metabolites from the endophytic fungus Lasiodiplodia theobromae

AU - Kamal, Nurkhalida

AU - Viegelmann, Christina V.

AU - Clements, Carol J.

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KW - anti-trypanosomal activity

KW - partial least square-discriminant analysis

KW - fractionation

KW - chemometrics

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