2020-09-302024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/652764The high-tech has improved the human welfare, and which also cause serious pollution simultaneously. The threats of the annual death caused by cancer are remaining high. The drug resistance of the pathogen is getting more serious due to the drug abuse, which results in the efficacy of the antibiotics being worse and worse. This problem has been developed as a global issue, and reducing the pollution and developing effective new drugs with no side effect seem to be of great urgency. Taiwan is located at tropical and subtropical region, where it is quite suitable for the growth of macroalgae. Especially, there are 67 kilometer along the north-east coast line of Taiwan, and the convergence of two ocean currents make the nutrients more abundant. The species diversity of local macroalgae is high, and of the over 200 species found, 179 species have been identified. The natural product research of the macroalgae has been performed for many years, and many novel compounds were reported successively. However, the chemical investigation of macroalgae-derived fungal strains remains rare. Thus, within three years this project is designed to focus on the natural product research of the macroalgae-derived fungal strains. After the fungal strains being isolated and purified, all the strains are subjected to screening using antimicrobial and anticancer platforms. Then, the active strains are mass cultured and studied on their active principles. The detail planning of the three years project is drawn up as below. In the first year, at least 1,500 fungal strains will be isolated from macroalgae. The crude extracts of the petri dish-cultured fungal strains will be subjected to antimicrobial and anticancer screening. Of all the strains screened, the bioactive strains will be identified by morphology and 18S rDNA. HPLC microfractionation coupled with UPLC/MS/MS will be performed for further dereplication. In the second year, the selected fungal strains that could produce novel compounds will be mass cultured. The media used for mass culture will be developed by an OSMAC method using different combination of the authentic nutrients. The bioactive compounds in the fermented products will be purified by a bioassay-guided method. All the obtained compounds will be identified by spectral analysis and subjected to pharmacological studies intensively. In the third year, in addition to follow the works of the 2nd year more chemical analogues of the bioactive compounds will be afforded by changing the culturing conditions of the fungal strains. Bioactive compounds with large amount will be modified for further structure-activity relationship studies. Moreover, all the obtained compounds will be subjected to pharmacological studies including antimicrobial, anti-inflammatory and antiangiogenesis. Hopefully, some leading drugs can be developed from the isolated fungal strains.macroalgae; endophytic fungi; bioactive natural products; fermentation; new drug development