碩士 / 國立陽明大學 / 生命科學系暨基因體科學研究所 / 101 / Traditionally, higher plants and terrestrial microorganisms are the richest sources of natural drugs that are for the treatment of fatal diseases such as cancer. Marine microorganisms have been proven to be a promising source of bioactive substances and some of them are expected to serve as lead compounds for drug development or pharmacological tools for the studies of biochemical processes in living cells. The marine environment is still an unexplored source for isolation of the discovery of novel natural products from microbes, including bacteria and microalgae.
During our studies on bioactive metabolites from marine microorganisms, we found that the ethylacetate extract of a marine bacterium strain ZS-2x showed significant cytotoxicity in vitro against human tumor cell lines. The ZS-2x was identified as Zooshikella sp. by the 16s rDNA technique, a gram-negative, strictly aerobic, red-pigment-producing marine bacterium. Bioassay-guided fractionation resulted in the isolation of seventeen compounds (1-17). Compound 1 (prodigiosin) 、2 (2-methyl-3-hexyl prodigiosin) and 3 (2-methyl-3-heptyl prodigiosin) are the prodiginines with tripyrroles. The compounds 4 to 10 are novel long-chain N-acyltyrosine derivatives, and are isolated from lab-cultured bacterium the first time. These types of N-acyltyrosine derivatives only can be identified by using the environmental DNA method, which isolated DNA directly from environmental DNA (eDNA), making eDNA cosmid libraries in E. coli, and screening the cosmid libraries for clones that have the ability to biosynthesize bioactive natural products. Compound 11 is a novel depsipeptide. Cmpound 12 is a indole, and be produced by bacteria as a degradation product of the amino acid tryptophan. Compounds 13 to 17 are dipketopiperazines, which are consist of dipeptides. The structures were determined by 1D- and 2D-NMR and mass spectrometry (MS). Compund 1、2、3、12 and 17 pereserve cancer cell inhibitory effects based on the MTS ( 3-( 4,5-dimethylthiazol-2-yl )-5-( 3-carboxymethoxyphenyl )-2-( 4-sulfophenyl )-2H-tetrazolium ) assay results, and new compound 10 and 11 pereserve H146 cell inhibitory effects. The IC50 value of these 2 compounds are 10.26 and 9.17M, respectively.
| Identifer | oai:union.ndltd.org:TW/101YM005105044 |
| Date | January 2013 |
| Creators | Yun-Ting Wu, 吳韻婷 |
| Contributors | Chung-Kuang Lu, 盧重光 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 152 |
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