Fusarielins

Fusarielins are produced by the fusarielin cluster harboring the polyketide synthase 9 (PKS9). By overexpressing the cluster specific transcription factor for PKS9 we successfully activated the cluster, which led to production of three novel fusarielins from Fusarium graminearum F, G and H. Fusarielin A-F have previously been identified in two unidentified Fusarium species and from a F. tricinctum strain, but the ability of other Fusarium species to produce fusarielins is unknown. To examine the distribution of fusarielin in the Fusarium genus we found that only F. graminearum and F. tricinctum were able to produce fusarielins. In order to identify the synthase pathway for fusarielins, we have generated knock out mutants of every gene in the cluster in F. graminearum and analyzed intermediated products by HPLC and NMR.
Fusarielins showed a weak toxic effect against bacteria and most human cell lines except human breast cancer cells. Rather, fusarielins proved able to stimulate MCF7 cells through a binding to the estrogen receptor. Because of this stimulation, fusarielins are categorized as mycoestrogens in spite of the fact that fusarielins have very little structural similarity to estrogen.
To examine possible implications of fusarielins for human health, we quantified fusarielins in six wheat spikes inoculated with F. graminearum. The predominant analogue, fusarielin H, was found in all six heavily infected spikes at levels ranging from 392 – 1865 µg/kg (mean: 989 µg/kg). This shows that fusarielins can be produced during infection, although only at relatively small levels.