Bioinformatics-guided connection of a biosynthetic gene cluster to the antitumor antibiotic gilvusmycin
Bioinformatics-guided connection of a biosynthetic gene cluster to the antitumor antibiotic gilvusmycin
复制标题
生物信息学引导下生物合成基因簇与抗肿瘤抗生素吉尔维霉素的连接
DOI：
10.1093/abbs/gmy030
复制
发表时间：
2018
影响因子：
3.7
通讯作者：
Yuan Hua
中科院分区：
文献类型：
--
作者：
Wang Xu;Wu Sheng;Jin Wenbing;Xu Bin;Tang Gongli;Yuan Hua
从微生物中分离出的天然产物已成为人类、动物和农业药物的丰富来源。1928年，弗莱明从青霉菌中发现青霉素，开启了微生物药物时代。后来，土壤微生物学家瓦克斯曼开发了一种筛选过程，从放线菌中发现了链霉素和其他抗生素。这种传统的分离方法提供了今天使用的大多数抗生素，但经常导致已知化合物bbb的高再发现率。随着DNA测序技术的发展，近三十年来，科学家们对天然产物的生物合成途径进行了深入研究，总结出了多酮类、非核糖体肽、核糖体合成和翻译后修饰肽、氨基糖苷类、萜类和生物碱等几种天然产物的生物合成规律。到目前为止，已经有数百人与他们的编码基因[3]有关。然而，与已发现的大量天然产物（超过100万）相比，与编码基因相关的天然产物数量非常少。另一方面，对序列数据库中大量原核生物DNA信息的全基因组分析揭示了大量未被表征的天然产物生物合成基因簇（BGCs）。基因进化和水平转移研究表明，同源BGCs编码具有相似结构的化合物[6]。因此，生物合成研究可用于将DNA数据库中未知的BGC与已知的天然产物相关联。
Natural products isolated from microbes have served as a prolific source of human, animal, and agricultural drugs. In 1928, Fleming discovered penicillin from Penicillium notatum, which began the microbial drug era. Later, the soil microbiologist Waksman developed a screening process that led to the discovery of streptomycin and other antibiotics from actinomycetes. Such traditional isolation methods have provided most of the antibiotics used today, but frequently lead to high-rediscovery rates of known compounds [1]. With the development of DNA sequencing technologies, the past three decades have witnessed the endeavors of scientists to dissect the biosynthetic pathways of natural products, and many common biosynthetic rules have been summarized for several classes of natural products, such as polyketides, nonribosomal peptides, ribosomally synthesized and post-translationally modified peptides, aminoglycosides, terpenoids, and alkaloids [2]. So far, hundreds of them have been connected to their encoding genes [3]. However, the number of natural products that have been connected to their encoding genes is very small when compared with vast numbers of natural products discovered (over one million)[4]. On the other hand, genome-wide analysis of the huge trove of prokaryotic DNA information in sequence databases has revealed a vast number of natural product biosynthetic gene clusters (BGCs) uncharacterized [5]. Gene evolution and horizontal transfer studies revealed that homologous BGCs encode chemical compounds with similar structures [6]. Hence the biosynthetic studies can be used for correlating an unknown BGC in the DNA database with a known natural product.