烯二炔类抗肿瘤抗生素的生物合成
Biosynthesis of enediyne antitumor antibiotics.
作者信息
Van Lanen Steven G, Shen Ben
机构信息
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI, 53705.
出版信息
Curr Top Med Chem. 2008;8(6):448-59. doi: 10.2174/156802608783955656.
Abstract
The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures' means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027.
摘要
烯二炔聚酮化合物是从多种放线菌中分离出的次生代谢产物。所有成员都具有很强的抗癌和抗菌活性，随着两种烯二炔衍生物作为抗癌药物近期上市，烯二炔在临床应用方面的前景已得到验证。这些化合物的生物合成备受关注，因为烯二炔家族具有众多独特的结构特征。目前已克隆并测序了五种烯二炔的基因簇，为理解自然界生物合成此类复杂奇特分子的方式奠定了基础。本文综述了烯二炔生物合成研究的当前进展，重点介绍了模型烯二炔C-1027。
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本文引用的文献
1
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.一种产生线性多烯以启动烯二炔类抗肿瘤抗生素生物合成的磷酸泛酰巯基乙胺化聚酮合酶。
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1460-5. doi: 10.1073/pnas.0711625105. Epub 2008 Jan 25.
2
Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism.烯二炔类抗肿瘤抗生素C-1027的生物合成涉及分支酸代谢中的一个新分支点。
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):494-9. doi: 10.1073/pnas.0708750105. Epub 2008 Jan 8.
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Designer enediynes generate DNA breaks, interstrand cross-links, or both, with concomitant changes in the regulation of DNA damage responses.设计型烯二炔会导致DNA断裂、链间交联或两者皆有，并伴随DNA损伤反应调控的变化。
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17632-7. doi: 10.1073/pnas.0708274104. Epub 2007 Oct 31.
4
Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis.来自马杜拉放线菌ATCC 39144的马杜菌素生物合成基因簇的表征，支持烯二炔生物合成的统一范式。
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Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica.基因组测序揭示了热带盐孢菌这一海洋放线菌中的复杂次生代谢组。
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The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway.来自C-1027烯二炔抗肿瘤抗生素生物合成途径的L-酪氨酸2,3-氨基变位酶的结构。
Biochemistry. 2007 Jun 19;46(24):7205-14. doi: 10.1021/bi7003685. Epub 2007 May 22.
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Single chemical modifications of the C-1027 enediyne core, a radiomimetic antitumor drug, affect both drug potency and the role of ataxia-telangiectasia mutated in cellular responses to DNA double-strand breaks.C-1027烯二炔核心（一种放射模拟抗肿瘤药物）的单一化学修饰，既影响药物效力，也影响共济失调毛细血管扩张症突变蛋白在细胞对DNA双链断裂反应中的作用。
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