| 隐性次级代谢产物生物合成基因簇的激活及天然产物定向发现 |
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| 引用本文： | 侯路宽,李花月,李文利. 隐性次级代谢产物生物合成基因簇的激活及天然产物定向发现[J]. 微生物学报, 2017, 57(11): 1722-1734 |
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| 作者姓名： | 侯路宽 李花月 李文利 |
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| 作者单位： | 教育部海洋药物重点实验室, 中国海洋大学医药学院, 山东 青岛 266003,教育部海洋药物重点实验室, 中国海洋大学医药学院, 山东 青岛 266003;青岛海洋科学与技术国家实验室, 海洋生物学与生物技术功能实验室, 山东 青岛 266237,教育部海洋药物重点实验室, 中国海洋大学医药学院, 山东 青岛 266003;青岛海洋科学与技术国家实验室, 海洋生物学与生物技术功能实验室, 山东 青岛 266237 |
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| 基金项目： | 国家自然科学基金（31570032）；国家自然科学基金-山东省政府联合基金（U1606403） |
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| 摘 要： | 传统的"活性-化合物"天然药物发现方法导致大量已知化合物被重复分离,大大加剧了新药发现的难度。规模化基因组测序揭示了微生物基因组中存在大量的隐性(cryptic)次级代谢产物生物合成基因簇,如何激活这些隐性基因簇成为当今世界天然产物研究领域的难点与热点。本文从途径特异性和多效性两个角度综述了隐性生物合成基因簇激活策略;同时,对基因组信息指导下结构导向(structure-guided)的化合物定向分离技术进行了归纳。隐性基因簇的激活为定向发掘具有优良活性的新型天然产物提供了新的契机。
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| 关 键 词： | 激活 隐性生物合成基因簇 天然产物 定向发现 |
| 收稿时间： | 2017-05-19 |
| 修稿时间： | 2017-06-12 |
Activation of cryptic microbial biosynthetic gene clusters and structure-guided natural product discovery |
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| Lukuan Hou,Huayue Li and Wenli Li. Activation of cryptic microbial biosynthetic gene clusters and structure-guided natural product discovery[J]. Acta microbiologica Sinica, 2017, 57(11): 1722-1734 |
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| Authors: | Lukuan Hou Huayue Li Wenli Li |
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| Affiliation: | Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong Province, China,Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong Province, China;Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, Shandong Province, China and Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong Province, China;Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, Shandong Province, China |
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| Abstract: | Traditional bioassay-guided natural product discovery has led to re-isolation of a large quantity of known compounds, and thus dramatically stunted the process of drug development. Large-scale genome sequencing revealed the existence of numerous cryptic biosynthetic gene clusters in microbes, which have attracted increasing attention in the research field of natural product discovery. In this review, we summarized the strategies for activation of microbial cryptic gene clusters at pathway-specific and pleiotropic levels, and discussed trends in structural identification technologies used for genome-guided compound mining. Activation of cryptic gene clusters will open new era for effective discovery of novel bioactive natural products. |
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| Keywords: | activation cryptic biosynthetic gene cluster natural products structure-guided discovery |
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