Abstract:
Discovery of new drugs have shifted from plants sources to microorganisms due to the enormous
diversity of the latter. Marine endophytic fungi (MEF) is underexplored as compared to their
terrestrial counterparts for the discovery of anti-infection drugs. This study set out to identify and
develop novel antifungal compounds from marine endophytic fungi sources using yeast genomics
guided approach. Six priority marine fungal endophytes were fermented and the secondary
metabolites produced were extracted using ethyl acetate. Crude extracts and fractions from
solvent-solvent fractionation and chromatography were tested against S. cerevisiae and C.
albicans. Majority of the extracts showed satisfactory antifungal activity (zone of inhibition > 11
mm). Sequence analysis of the fungi ITS-rDNA revealed that the isolates belonged to three major
genera; Aspergillus, Clonostachys and Meyerozyma. An investigation of the mechanism of action
of the extracts from the 6 endophytes indicated that these extracts targeted protein synthesis,
ergosterol biosynthesis and RNA translation. The study also confirmed that production of bioactive
metabolites by marine fungal endophytes is time-dependent and favours shorter incubation of
fungal fermentation cultures. In vitro interactions of phenotype modulating compounds with either
standard antifungal drugs or fungal extracts resulted in novel synergistic interactions against
Candida albicans and Saccharomyces cerevisiae. Structural elucidation of the compounds in the
bioactive fractions using mass spectrometry (ms/ms) identified 22 novel chemical structures which
is anticipated to exhibit antifungal activity. Three fractions from MEF 134; 134 FD K1V1 V1, 134
FD K1V5V3 and 134 FD K2V3V5 were active against S. cerevisiae but not the pathogenic C.
albicans. This is an indication of an antitumor cytotoxic compound and not an antifungal. The
cytotoxicity effect of the three compounds against HepG2 cells was tested in a dose dependent
manner. It was demonstrated that several cancer, metabolism-related pathways and gene
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ontologies were regulated by the treatment with the 3 fractions from marine endophytic fungi. The
data generated in this study highlights the opportunities of exploring fungal endophytes as useful
sources of antifungal compounds for treatment of infections caused by pathogenic fungi.
