In Silico-Based Drug Discovery Targeting HGF-Met

Division of Tumor Dynamics and Regulatio

Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations

Division of Medical Oncology and Surgical Oncolog

腸内細菌による生理活性物質代謝の酵素学的解析と応用

京都大学0048新制・論文博士博士(農学)乙第12822号論農博第2795号新制||農||1025(附属図書館)学位論文||H26||N4817(農学部図書室)31309京都大学農学研究科食品生物科学専攻(主査)教授 喜多 恵子, 教授 三上 文三, 教授 栗原 達夫学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDFA

Biohydrogenation of C(20) polyunsaturated fatty acids by anaerobic bacteria.

The PUFAs include many bioactive lipids. The microbial metabolism of C18 PUFAs is known to produce their bioactive isomers, such as conjugated FAs and hydroxy FAs, but there is little information on that of C20 PUFAs. In this study, we aimed to obtain anaerobic bacteria with the ability to produce novel PUFAs from C20 PUFAs. Through the screening of ∼100 strains of anaerobic bacteria, Clostridium bifermentans JCM 1386 was selected as a strain with the ability to saturate PUFAs during anaerobic cultivation. This strain converted arachidonic acid (cis-5, cis-8, cis-11, cis-14-eicosatetraenoic acid) and EPA (cis-5, cis-8, cis-11, cis-14, cis-17-EPA) into cis-5, cis-8, trans-13-eicosatrienoic acid and cis-5, cis-8, trans-13, cis-17-eicosatetraenoic acid, giving yields of 57% and 67% against the added PUFAs, respectively. This is the first report of the isolation of a bacterium transforming C20 PUFAs into corresponding non-methylene-interrupted FAs. We further investigated the substrate specificity of the biohydrogenation by this strain and revealed that it can convert two cis double bonds at the ω6 and ω9 positions in various C18 and C20 PUFAs into a trans double bond at the ω7 position. This study should serve to open up the development of novel potentially bioactive PUFAs