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2013 , Vol. 33 >Issue 06: 1326 - 1332

DOI: https://doi.org/10.6023/cjoc201212046

研究论文

越野他汀生物合成介导的海洋小单孢菌中一个新天然产物的发现

  • 李慧 ,
  • 周强 ,
  • 唐玉敏 ,
  • 赵圣印 ,
  • 唐功利
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  • a 东华大学化学化工与生物工程学院 上海 201620;
    b 中国科学院上海有机化学研究所 生命有机国家重点实验室 上海 200032

收稿日期: 2013-12-27

  修回日期: 2013-02-19

  网络出版日期: 2013-03-01

基金资助

国家自然科学基金(No.81102337)资助项目.

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Discovery of a New Natural Product from Marine-Derived Micro- monospora Guided by the Biosynthetic Studies of Kosinostatin

  • Li Hui ,
  • Zhou Qiang ,
  • Tang Yumin ,
  • Zhao Shengyin ,
  • Tang Gongli
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  • a College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620;
    b State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received date: 2013-12-27

  Revised date: 2013-02-19

  Online published: 2013-03-01

Supported by

Project supported by the National Natural Science Foundation of China (No.81102337).

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摘要

越野他汀(kosinostatin, KST)是从海洋小单孢菌Micromonospora sp.TP-A0468中分离得到的一种具有良好抗肿瘤活性的蒽环类抗生素.在对越野他汀生物合成基因簇的研究中, 构建了3,5-差向异构酶基因kstD3的基因中断突变株mKOSD3, 该菌株中一种新的天然产物因产量较野生型有所提高而被发现.分离新化合物并进行结构鉴定, 结果显示该化合物是异醌环素B C-3"位脱氧的结构类似物, 命名为脱氧异醌环素B.生物活性测试表明, 相比于异醌环素B, 其体外细胞毒性明显降低.进一步的基因敲除实验发现, 基因簇中的kstD5编码的是一个对糖基底物识别不专一的糖基转移酶, 这为利用该酶的特性获得更多蒽环类衍生物奠定了基础.

关键词： 天然产物; 脱氧异醌环素B; 糖基转移酶; 底物容忍性

本文引用格式

李慧 , 周强 , 唐玉敏 , 赵圣印 , 唐功利 . 越野他汀生物合成介导的海洋小单孢菌中一个新天然产物的发现[J]. 有机化学, 2013 , 33(06) : 1326 -1332 . DOI: 10.6023/cjoc201212046

Abstract

Kosinostatin (KST), isolated from the fermentation extraction of Micromonospora sp.TP-A0468, is a kind of anthraquinones antibiotic with antitumor activity.To investigate the function of kstD3 gene, encoding a sugar 3,5-epimerase involved in the KST biosynthetic gene cluster, the gene disruption mutant strain Micromonospora sp.TP-A0468 mKOSD3 is constructed.A novel compound, deoxy-isoquinocycline B was discovered and isolated from this mutant strain and its structure was characterized by comparison to the HRMS and NMR spectra of isoquinocycline B.This compound could be considered as an analogue of isoquinocycline B.Compared with isoquinocycline B, its antitumor activity decreased significantly.It is also found that the glycosyltransferase KstD5 is more substrate-flexible than anticipated, which lay the foundation for further using the characteristics of this enzyme to obtain more analogues.

Key words： natural product; deoxy-isoquinocycline B; glycosyltransferase; substrate-flexibility

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