Mining Of Three Natural Products From Fungi

In this paper,three strategies-changing culture conditions,overexpression of transcriptional regulation factor and heterologous expression were used to find and isolate new secondary metabolites(SMs)from Myceliophthora thermophila and Cordyceps militaris,and the properties of the isolated compounds were preliminarily tested.The main results are as follows:1.By changing the culture temperature,one compound not reported in the literature was isolated at 37? from M.thermophila.In the 5-L fermentors,it was liquid fermented for 7 liters,and the compound was purified.The high resolution mass spectrometry showed that the molecular formula of the compound is C26H39NO4,with a molecular weight of 429.Nuclear magnetic resonance(NMR)showed that the compound was a derivative of Myceliothermophin A,except it had a-OH on 8-C.Like Myceliothermophin A,it also had toxic effects on cancer cell lines.It exhibited IC50 value of 1.47 ?g/mL toward DLD-1,1.66?g/mL toward Hep3B,1.73 ?g/mL toward HepG2 and 0.32 ?g/mL toward HGC.2.By overexpressing the transcriptional regulator(TF),the NR-PKS gene cluster was successfully activated which was previously silent in M.thermophila.Two compounds,microsphaeropsones A and xanthepinone,were isolated and purified by solid fermentation for 5 L,and the molecular weights were 334 and 332,respectively.Xanthepinone had the ability to inhibit Bacillus subtilis and Yeast.3.Previously,our laboratory had fermented the C.militaris,but we did not isolate anything from it.However,through genome prediction,we found that it encoded at least 28 possible gene clusters of secondary metabolites,indicating the potential value of its development.A new compound was obtained by a predicted PKS-NRPS related gene cluster of C.militaris through the heterologous expression in Aspergillus niulans.The molecular formula of the compound was C28H39NO5,with a molecular weight of 469.The bacteriostasis experiment only showed that the compound had inhibition on B.subtilis,,and the antitumor activity test showed that the compound had no obvious cytotoxicity.