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基于基因组挖掘的新型生物活性天然产物的发现

Discovery of novel bioactive natural products driven by genome mining.

作者信息

Li Zhongyue, Zhu Deyu, Shen Yuemao

机构信息

Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University.

School of Basic Medical Sciences, Shandong University.

出版信息

Drug Discov Ther. 2018;12(6):318-328. doi: 10.5582/ddt.2018.01066.

DOI:10.5582/ddt.2018.01066
PMID:30674766
Abstract

Microbial natural product is an important source for drug discovery. As more and more microbial genomes are sequenced, bioinformatics analysis shows that there are huge resources of novel natural products. Genome mining is a new strategy of natural product discovery based on gene cluster sequences and biosynthetic pathways. At the same time, it can directly associate the structures of natural products with synthetic pathways, and facilitate the study of biosynthesis and combinatorial biosynthesis. In this paper, the strategies of genome mining, including bioinformatics predictions, metabolomic comparisons and genetic manipulations, are reviewed, which shows a great advantage of this strategy in exploiting the potential of microbial natural products. With the development of genome mining methodology and techniques, it will be possible to realize rational exploitation of microbial natural product resources.

摘要

微生物天然产物是药物发现的重要来源。随着越来越多的微生物基因组被测序,生物信息学分析表明存在大量新型天然产物资源。基因组挖掘是基于基因簇序列和生物合成途径的天然产物发现新策略。同时,它能直接将天然产物的结构与合成途径联系起来,便于生物合成和组合生物合成的研究。本文综述了基因组挖掘策略,包括生物信息学预测、代谢组学比较和基因操作,显示了该策略在开发微生物天然产物潜力方面的巨大优势。随着基因组挖掘方法和技术的发展,实现微生物天然产物资源的合理开发将成为可能。

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