The Secondary Metabolites And Antimicrobial Activities Of Two Gorgonian-derived Fungi From The South China Sea

Marine microorganisms, which are well known for the extremely rich species diversity and the outstanding biologically activities, have become significant resources for drug discovery in recent years. Marine microorganisms have proven to be a rich source of structurally novel and special pharmacological active secondary metabolites, including quinones, terpenoids, alkaloids, which exhibited promising application for the antibacterial, anti-tumor and antiviral effects. In present study, the secondary metabolites from two gorgonian-derived fungi collected from the South China Sea were isolated and identified under the guidance of antimicrobial activity, in order to obtain antimicrobial activity compounds. The results also provide an important research idea for the discovery and screening of marine lead compounds and the marine nature products from the marine microorganism.A gorgonian-derived fungus Micro sphaeropsis sp. RA10-14 and Aspergillus sp. XS-20090066, which was induced by chemical epigenetic modification method, were chosen for the chemical investigation under the guidance of bioassay. From cultures of these fungi,23 compounds were isolated from the active fungal fermentation by column chromatography on si-gel, Sephadex LH-20, and semi-HPLC, and identified by spectroscopy methods of NMR, MS, IR, UV, CD, combined with a variety of chemical methods.Eleven fungal metabolites, including three polyketide compounds (1-3), four chromones (4-7), two isocoumarins (8,9), one coumarin (10), together with one orcinol (11), were obtained from the gorgonian-derived fungus Microsphaeropsis sp. RA10-14, collected from the South China Sea. Among them, compounds 1-5 were new compounds. Compounds 1 and 2 were a pair of C-11 epimers. The preliminary study of biosynthetic pathway suggested this type compounds were transformed from the anthraquinones. The relative configurations of 1 and 2 were elucidated by 1D NOE experiments and the coupling constant calculation. And the absolute configurations were assigned by the modified Mosher’s method.All of these compounds were evaluated for antibacterial activities. Among them, compound 1 exhibited significant inhibitory activity against P. aeruginosa, N. brasiliensis, K. rhizophila, B. megaterium, with the MIC values of 0.19,0.19,0.19, 0.19μM, which were equal to the positive control ciprofloxacin. Interestingly, compound 2, with a opposite configuration at C-11, exhibited weak activity, suggesting that the configuration at C-11 might affect the antibacterial activity. Copound 9 exhibited significant inhibitory activity. Compound 8 did not express any significant antimicrobial activity, which indicated that pyran group might play an important role in enhancing the antibacterial activity of these three compounds. Additionally, compounds 1 and 2 exhibited moderate antifungal activity. Miniaturized microalgal growth-inhibition bioassay model were used to evaluate bioactivities. The results indicated that 1-3 showed moderate growth-inhibition activity towards Platymonas helgolandica.Investigation on the gorgonian-derived fungus Aspergillus sp. (XS-2009-0066) using the chemical epigenetic perturbation method, led to the isolation of six bisabolane-type sesquiterpenoids (12-17) and compounds (18-23), which were isolated from the same fungus in our previous study. The antibacterial activities of all isolated compounds were evaluated with nine pathogenic bacteria strains. Compound 14 showed pronounced antibacterial activity against Staphylococcus aureus with an MIC value of 3.13 μM. Interestingly, compound 17, with a carboxyl group at C-7, exhibited weak activity against S. aureus, suggesting that the hydroxymethyl group at C-7 in this type compounds might be a functional group.In conclusion, several kinds of compounds were isolated from the two gorgonian-derived fungi under the guidance of antimicrobial activity. Most of these metabolites showed the promising antimicrobial activities, providing the basic information for the development and application of antibacterial drug lead compounds. In addition, silent gene clusters of marine-derived fungi were succeeded to activate using chemical epigenetic modification method, producing more secondary metabolites.