Bioactive Metabolites from the Deep Subseafloor Fungus Oidiodendron griseum UBOCC-A-114129

Abstract

Four bioactive compounds have been isolated from the fungus Oidiodendron griseum UBOCC-A-114129 cultivated from deep subsurface sediment. They were structurally characterized using a combination of LC-MS/MS and NMR analyses as fuscin and its derivatives (dihydrofuscin, dihydrosecofuscin, and secofuscin) and identified as polyketides. Albeit those compounds were already obtained from terrestrial fungi, this is the first report of their production by an Oidiodendron species and by the deepest subseafloor isolate ever studied for biological activities. We report a weak antibacterial activity of dihydrosecofuscin and secofuscin mainly directed against Gram-positive bacteria (Minimum Inhibitory Concentration (MIC) equal to Minimum Bactericidal Concentration (MBC), in the range of 100 μg/mL). The activity on various protein kinases was also analyzed and revealed a significant inhibition of CDC2-like kinase-1 (CLK1) by dihysecofuscin.

Keywords: anti-kinase; antibacterial; bioactivities; deep subseafloor fungi.

Figure 1

Reverse phase-high-performance liquid chromatography (RP-HPLC) analysis of the F10–90 fractions. Elution was performed using a linear gradient of acetonitrile ACN + 0.07% trifluoroacetic acid (TFA) (blue line). The chromatogram represents the max plot recorded between 220 and 600 nm. Peaks exhibiting antimicrobial activity are overlaid in green. Bioactive compounds were numerated according to their elution order.

Figure 2

Chemical structures of the bioactive compounds produced by Oidiodendron griseum CB_36.

Figure 3

Kinetics of O. griseum UBOCC-A-114129 growth ($●$) and of fuscin and derivatives production resulting from three independent experiments. The latter were quantified by the area below the elution peak detected by RP-HPLC after solid-phase extraction (SPE) extraction of the cell-free supernatant. $■$: Dihydrosecofuscin, $♦$: fuscin and dihydrofuscin, $▲$: secofuscin.

Figure 4

Effect of diyhdrosecofuscin on the catalytic activity of Mm_CLK1. Recombinant GST-CLK1 was assayed in the presence of increasing concentrations of diyhdrosecofuscin. Kinase activities are expressed in % of maximal activity, i.e., measured in the absence of inhibitor (mean ± standard deviation (SD), n = 3).