Research on Secondary Metabolites and Their Biological Activities in Solid Fermentation Products of Deep Sea Fungus Neoroussolella sp
Marine microorganisms have evolved different metabolic systems and defense mechanisms from terrestrial organisms due to their long-term exposure to extreme environments such as high salt, high pressure, low temperature, low light, and oligotrophic levels. As a result, the secondary metabolites they produce are highly complex and diverse. Marine microbial sources have an extremely rich variety of natural products, covering almost all structural types of natural products and possessing a wide range of biological activities, making them an important source of lead compounds for new natural medicines. Studying the secondary metabolites of marine microorganisms will enable the discovery of lead compounds with novel chemical structures and significant biological activities, providing important model structures and drug precursors for new drug research and development.

Our research group has previously isolated and identified fungi from sediments at a depth of 4314m in the South China Sea (114 ° 34 ′ 32 ″ E, 13 ° 57 ′ 27 ″ N), and obtained a novel marine fungus Neoroussolella sp. According to literature review, there are currently no reports on the research of secondary metabolites both domestically and internationally. Through HPLC-MS analysis of the crude extract obtained from small-scale liquid fermentation, it was found that its metabolites were very abundant. Based on this, we used normal silica gel column, gel column, high performance liquid chromatography and other chromatographic techniques to systematically study the chemical composition of this fungus.

Neoroussolella is a new genus of fungi first discovered and described by Liu et al. in 2014. At present, the Neoroussolella genus fungi that have been isolated and identified mainly come from plants and exist in bamboo, herbaceous plants, and palm trees, while there are few reports of marine sources, mainly concentrated in the Mediterranean basin, and all sources are from benthic plants. The FS526 strain used in this study was isolated from deep-sea sediments in the South China Sea. According to literature research, there have been no reports on the secondary metabolites of this genus of fungi.

This study identified for the first time 15 monomeric compounds from the solid fermentation products of the deep-sea fungus Neoroussolella sp.FS526, with diverse structural types including 2 terpenes, 5 isocoumarins, 2 benzofurans, 1 monoterpene, and 5 phenol derivatives. All compounds were isolated from Neoroussolella genus fungi for the first time. Based on the structural types of these compounds, it is speculated that phenol and its derivatives are the main characteristic secondary metabolites of this fungus, which are mainly produced through the polyketide biosynthesis pathway. Compound 1 has structural analogues with different C-9 configurations. The S configuration of this structural type was first discovered by Stierle et al. from Penicillium fungi and named Berkeleyacetal C. This compound has inhibitory effects on non-small cell lung cancer cell lines. Later, Sun et al. also discovered Berkeleyacetal C from Penicillium purpurogenum MHZ 111. Subsequently, Chen et al. isolated and purified a new structural analogue with C-9 R configuration from Talaromyces amettolkiae YX1, and named it amettolkolide B. Activity tests were conducted on two different configurations of monomer compounds, Berkeleyacetal C and Amestolkolide B, both of which showed strong NO production inhibition activity, but no significant cytotoxic activity was found. The biological activity test results of this study showed that compound 1 has weak cytotoxic activity. In addition, compound 7 of isocoumarin has strong antioxidant activity, and its IC50 value is close to the positive control Vc, which is worthy of further research. The results of this study enrich the chemical composition of Neoroussolella fungi and provide a material basis for further research on other biological activities in the future.