由五種不同屬之十三株軟珊瑚(8株野外採集與5株養殖)中篩選具抗菌活性海洋細菌，珊瑚採自於台灣墾丁南灣海域，五株養殖軟珊瑚採集後穩定養殖於開放式循環海水系統之水缸半年以上。分別從野外採集與養殖軟珊瑚中各分離出1526株與1138株細菌，並測試其海水需求性與抗菌活性。經分析顯示野外採集與養殖珊瑚具海水需求菌株和海水需求菌株中具抗菌活性菌株之比例沒有顯著差異。另外選擇19株抗菌活性較佳之細菌進行16S rRNA序列的分析。根據16S rRNA序列比對從珊瑚分離出的細菌，其中3株細菌僅能辨識至Rhodobacteraceae科，16株細菌分別屬於8個菌屬，包括Marinobacterium (2)、Pseudoalteromonas (1)、Tateyamaria (1)、Vibrio (1)、Listonella (1)、Enterovibrio (1)、Tateyamaria (1)、Labrenzia (2)與Pseudovibrio (4)。
從珊瑚衍生細菌Pseudoalteromonas sp. CGH2XX分離出三個新化合物pseudoalteromones A–C (1–3)與兩個已知diketopiperazine類型化合物cyclo(L-proline-L-alanine) (4)與cyclo(L-proline-L-tyroine) (5)。從海綿衍生放線菌Streptomyces sp. GIC10-1分離出三個新化合物bafilomycins M–O (6–8)，與10個已知化合物，包括5個bafilomycin類型化合物(9–13)、4個elaiophylin類型化合物(14–17)與1個polyether類型化合物nigericin (18)。從海洋底泥細菌Bacillus amyloliquefaciens strain IA-LB中分離出lipopeptide類化合物iso-C13-surfactin (19)。actinomycin D (20)為蒂殼海綿衍生放線菌S. massaporeus strain AIAC1-21主要抗菌與細胞毒殺活性成份。
化合物1、6–18和20能抑制K-562癌細胞株生長，2–5則不具細胞毒殺活性。化合物 1、16、18與20對S. aureus具抗菌活性，化合物2、5與19則不具抗菌活性。化合物19對於fMLP誘導人類嗜中性白血球產生超氧陰離子與彈性蛋白酶的釋放具有顯著抑制的活性，然而無法抑制MMK-1誘導之發炎反應，1與2對fMLP誘發人類嗜中性白血球超氧陰離子產生與彈性蛋白酶的釋放具微弱抑制的活性。
本研究證實野外與養殖軟珊瑚衍生細菌同樣具有抗菌活性，從珊瑚衍生細菌Pseudoalteromonas sp. CGH2XX分離出新的二次代謝產物，從海綿衍生菌Streptomyces sp. GIC10-1中分離出具有良好抗癌活性的新天然物，以上均顯示海洋細菌具有許多未知天然物，是為一個具有潛力的生物活性天然物來源。

Screening of marine bacteria with antibacterial activity from thirteen (eight wild type and five cultured type) corals belonging to five different genera were collected from Nanwan Bay (southern Taiwan), while the five cultured corals were kept in an open seawater recirculating aquaculture system over than half year. A total of 1527 and 1138 bacterial strains were isolated from wild and cultured corals, respectively, and were assessed for seawater requirement and antimicrobial activity. The data showed that there is no difference on the ratio of seawater-requiring bacteria between wild and cultured corals, and neither did the ratio of antibiotics producing bacteria within the seawater-requiring bacteria differ between the corals. Nineteen bacteria with high antimicrobial activities were identified via 16S rRNA sequencing. Only three strains could be assigned to the family Rhodobacteraceae. The other 16 strains belong to eight genera: Marinobacterium (2), Pseudoalteromonas (1), Vibrio (4), Listonella (1), Enterovibrio (1), Tateyamaria (1), Labrenzia (2), and Pseudovibrio (4).
Three new compounds, pseudoalteromones A–C (1–3), along with two known diketopiperazines, cyclo(L-proline-L-alanine) (4) and cyclo(L-proline-L-tyrosine) (5), were isolated from coral-derived bacterium Pseudoalteromonas sp. CGH2XX. Three new compounds, bafilomycins M–O (6–8), along with five bafilomycins (9–13), four elaiophylins (14–17), and a polyether type compound, nigericin (18), were isolated from Streptomyces sp. GIC10-1. One known lipopeptide, iso-C13-surfactin (19), was isolated from a bacterium Bacillus amyloliquefaciens strain IA-LB isolated from marine sediment. Actinomycin D (20) was the main bioactivity compound of the sponge-derived actinobacterium S. massaporeus strain AIAC1-21.
Compounds 1, 6–18, and 20 were found to exhibit cytotoxicity toward K-562, tumor cells; compounds 2–5 show no cytotoxicity. Compounds 1、16、18 and 20 were found to exhibit antibacterial activity toward Straphylococcus aureus; compounds 2, 5 and 19 show no antibacterial activity. In human neutrophils, compound 19 had significant inhibition effects on the release of superoxide and elastase induced by fMLP, but not MMK-1. Compounds 1 and 2 displayed the weak inhibition on the release of superoxide and elastase.
In this study, we demonstrate that wild and cultured soft coral-derived bacteria displayed the same antibacterial activities. We separated new secondary metabolite from soft coral-derived bacterium Pseudoalteromonas sp. CGH2XX and new cytotoxic natural products from sponge-derived bacterium Streptomyces sp. GIC10-1. The study above presents that marine bacteria contain many unknown natural products. Thus has made marine bacteria a potential source of bioactive natural products.

第一章 緒論 1
第二章 實驗方法 57
第一節 樣本來源與採集 57
第二節 珊瑚衍生細菌分離培養 58
第三節 海水需求與含抗菌活性菌株之篩選 59
第四節 以16S rRNA序列鑑定細菌之分類地位 62
第五節 萃取物抗菌、細胞毒殺與抗發炎活性分析 67
第三章 結果與討論 81
第四章 結構解析與生物活性 121
第一節 海洋細菌Pseudoalteromonas sp. CGH2XX所含天然物之結構解析 121
第二節 Streptomycetes sp. GIC10-1所含天然物之結構解析 157
第三節 Bacillus amyloliquefaciens strain IA-LB所含天然物之結構解析 248
第四節 海洋細菌Streptomyces massaporeus AIAC1-21所含天然物之結構解析253
第五節 化合物實驗數據整理 260
第六節 生物活性數據 263
第五章 結論 269

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