The Secondary Metabolites From Two Marine Symbiotic Fungi And Their Chemical Ecological Effects

Because of the particularity and the potentially medicinal values in thedevelopment of marine drugs, the related research of marine microorganisms has beenpaid close attention in recent years. The unique living conditions of marinemicroorganisms including high-pressure, high-salt, anaerobic and closed-ray, urgedmicroorganisms to produce a series of structurally novel and biologically activesecondary metabolites. Especially, during the close relationships and mutual effectsbetween the symbiotic microorganisms and their hosting t marine invertebrates, whichare lack of physical defense, microorganisms may accumulate and produce secondarymetabolites with chemically defensive effects to protect their hosts. More increasingattentions have been paied by the scientists in the fields of natural medicinalchemistry, chemical ecology, chemical taxonomy, and pharmacology.In this thesis, the secondary metabolites of one sponge-derived and one softcoral-derived fungi were investigated using the research methods of marine naturalproducts and modern spectroscopic technologies, together with the optimized methodof the microbial fermentation conditions. The biological activities of the isolatedcompounds were evaluated on the models of antibacterial, and antifouling activities.The chemical ecological relationship between marine microorganisms and their hostswas also discussed primarily.The secondary metabolites were isolated from the fermentation broth ofsponge-derived fungus Aspergillus sp.(L14-1’) from the South China Sea, of whichthe EtOAc extract showed antibacterial activity. The structures of ten pure compoundsincluding five bisabolane sesquiterpenoids, four benzene derivatives, and oneisocoumarin, were elucidated as aspergiterpenoid A (1),()-sydonol (2),()-sydonicacid (3),(-)-5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol(4),8-hydroxy-3-(4-hydroxypentyl)isochroman-1-one (5), (Z)-5-(hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol (6),3-methoxyphenol (7),4-methylbenzene-1,3-diol (8),5-methylbenzene-1,3-diol (9), and4-methoxybenzene-1,2-diol (10). Compounds15are new compounds. The absolute configurations of thebisabolane sesquiterpenoids were opposite to those of compounds isolated from acoral-derived fungi Aspergillus sp. by our group. This type of compounds withopposite stereochemistries had also been reported from corals and sponges by othergroups. These facts suggested that the similar compounds with oppositestereochemistry might be produced by the fungi originated from the different marineorganisms using the similar biogenic synthesis pathway; and microorganisms maybethe real producers of these compounds. The biological activities of the isolatedcompounds were evaluated primarily on the models of antibacterial, and antifoulingactivities. Compounds1~4,6showed antibacterial activity, of which compound4showed selective antibacterial activity against S. albus and B. subtilis with the MICvalues of5.00and2.50μM, respectively, and compound3showed a broad spectrum ofantibacterial activity toward four pathogenic bacteria and uniquely against two marinebacteria, especially to S. lutea with the MIC value of2.50μM, which was similar to thepositive control ciprofloxacin. Compound4also exhibited antifouling activity againstthe larval settlement of barnacle Balanus amphitrite, with a inhibitory rate of100%at aconcentration of25.0μg/mL. These results suggested that the bisabolanesesquiterpenoids may play a positive role in the chemical defenses of its host sponge.A soft coral-derived fungus Pestalotiopsis sp.(7-6) from the South China Sea, ofwhich the EtOAc extract showed significant antibacterial activity, was fermented andextracted. Eleven compounds were isolated from the fermentation mycelia, and theirstructures of these compounds including4chlorinated benzophenones,4substitutedbenzenes methyl rhamnosides,2sterides and1anthraquinone were determined ascompound11, pestalachloride C (12), pestalachloride A (1a,1b)(13,14), compound15, compound16, compound17, compound18,(22E,24R)-ergosta-7,9,22-trien-3β-ol(19),(22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,22-dien-3β-ol (20), and emodin(21). Compounds11,15~18are new compounds. It should be noted that compound11which possesses the closely zero of the optical rotation value, should be a pair ofenantiomers,. This deduction was verified by the chirial HPLC analysis and singlecrystal X-ray diffraction data. In the premilary antibacterial and cytotoxic experiments, only compounds11and12showed weak antibacterial activity.In this study, the secondary metabolites from two marine-drived fungi were isolatedand their structures were identified, and their biological activities were also evaluated.The chemical ecological effects of the secondary metabolites from symbiotic fungiwere also discussed primarily. The results should provide an important research ideafor the discovery of marine lead compounds from the marine microorganism and alsosupply with the valuable information for further reaearch on the relationships betweenmarine symbiotic microorganisms and their hosts.