The Screening For Bioactive Strains From Marine-derived Actinomycetes And The Study On The Secondary Metabolites From Strain 1023

Marine-derived actinomycetes are the great component element of microbe in marine. There are innumerable kinds of marine-derived actinomycetes, which distribute widely in all kinds of marine environment. Marine-derived actinomycetes might produce different types of bioactive compounds. They are a prolific and extraordinary resource for the discovery of new drugs.This thesis covers preliminary study on the antibacterial, cytotoxitic and AChE inhibitory activity of 13 marine-derived actinomycetes. Furthermore, we investigated the metabolites of the one of them, the strain 1023, which exhibited potent antitumor activities. The goal of this thesis research was to exploit novel bioactive secondary metabolites that will continue to be an important source of new medicines.We cultured the 13 marine-derived actinomycetes with three different media, then investigated the antibacterial, cytotoxic and AChE inhibitory activities for crude extracts of them. The result showed that 92.3 % of the total extracts inhibited the AChE acitivity by more than 50 % at 100μg/mL. There were 20.5 % and 5.1 % of the total extracts showed antibacterial activity against Escherichia coli and Bacillus subtilis respectively. There were 14 extracts (35.9 % of the total extracts) showed cytotoxic activity against KB or HepG2 cell lines, among them, strain 1023 was found to have potent cytotoxic activitiy, three extracts of that inhibited the proliferation of KB by more than 60 % at 20μg/mL.Taxonomic studies, including morphological study and using sequence analyses of the 16SrDNA and matching of the resulting sequence against the database, indicated that strain 1023 belongs to the Streptomyces genus.We studied the metabolites from the strain 1023. Employing Silica gel Column Chromatography, middle-pressure reversed phase liquid Chromato- graphy, Sephadex LH-20 Dextran gel Chromatography and re-crystal, we isolated eight compounds (mPm7, HWX13, HWX23, HWX27, HWX29, HWX33, HWX35, HWX39) from the strain. The structures of the eight compounds were identified. The structure of mPm7 is valinomycin, and the other seven compouds are nonactic acid and its derivatives. The structures of HWX13, HWX27, HWX29, HWX33, HWX35 and HWX39 were identified as homononactic acid, Feigrisolide C, nonactic acid acetate, homononactic methylester, nonactic methylester and nonactic acid respectively. HWX23 was identified as methyl 2-(5-(3-hydroxybutyl)-tetrahydrofuran-2-yl) propanoate,which is a new compoud.In the later investigation of antitumor and antimicrobial activities, mPm7 showed potent cytotoxicity to the human cervical cancer cell line Hela (IC50 3.04 ng/mL). This compound showed potent antifungal activity against Candida albicans with MIC of 1.56μg/mL and also inhibited Saccharomyces cerevisiae (MIC = 6.25μg/mL). The other 7 compounds showed no bioactivity in our test.Our study indicated that marine-derived actinomycetes were reliable resources for nove metabolites with antitumor and antimicrobial bioactivity. They are a unique suorce for new medicines.