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    當前位置 > 首頁 > 新聞動態 > 科研動態
    成都生物研究所在喜樹堿生物合成研究中獲新進展
    更新日期: 2019-07-05 作者: 李偉 文章來源:天然產物與臨床轉化重點實驗室
    打印 文本大小:    

     喜樹堿(Camptothecin),是從我國特有植物喜樹中分離鑒定的單萜吲哚生物堿,具有獨特的抗腫瘤作用機理,其衍生物拓撲替康、伊立替康等是用于治療小細胞肺癌、卵巢癌等幾十種常見腫瘤的藥物。 

     中國科學院成都生物研究所天然產物與臨床轉化重點實驗室羅應剛課題組于近期通過分析、挖掘喜樹的轉錄組數據,發現了具有雙催化功能的細胞色素P450CYP72A565CaCYP72A610:它們催化loganinC-7C-8之間的C-C鍵斷裂反應,生成相應的secologanin。不同于之前報道的長春花CrSLS只能接受loganin為底物,CYP72A565CaCYP72A610還可催化loganic acid發生C-C鍵斷裂生成secologanic acid。進化樹分析結果顯示該兩P450s與報道的CrDL7H在親緣關系上非常近,且序列相似度也較高,作者推測CYP72A565CaCYP72A610可能具有CrDL7H相同的催化活性。結果顯示,CYP72A565CaCYP72A610的確可以催化7-deoxyloganic acid發生區域和立體選擇性地C-7位羥基化反應生成loganic acid,與報道的CrDL7H的催化功能一致。因此,CYP72A565CaCYP72A610是具有催化7-deoxyloganic acidC-7羥化和loganic acid / loganinC7-C8之間C-C鍵斷裂反應的新穎雙功能P450酶,參與了喜樹堿生物合成過程中的兩步連續反應。 

     比較代謝組分析結果表明loganic acidsecologanic acidstrictosidinic acid存在于喜樹各組織中,而loganinsecologaninstrictosidine在此條件下并未檢測到。 

     該工作的完成不僅發現了具有新穎雙功能的P450酶,同時也為喜樹堿的生物合成過程研究提供了重要參考。該工作以題為《Bifunctional Cytochrome P450 Enzymes Involved in Camptothecin Biosynthesis》發表于ACS Chemical Biology2019, 14, 6, 1091-1096. DOI: 10.1021/acschembio.8b01124。該工作得到了國家自然科學基金(21172216)、中國科學院(ZSTH-003)和四川省應用基礎研究(2015JY0058)等項目的資助。 

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