用于基因组学引导的天然产物发现的直接捕获技术

Direct Capture Technologies for Genomics-Guided Discovery of Natural Products.

作者信息

Chan Andrew N, Santa Maria Kevin C, Li Bo

机构信息

Department of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, NC, 27599, USA.

出版信息

Curr Top Med Chem. 2016;16(15):1695-704. doi: 10.2174/1568026616666151012111209.

Abstract

Microbes are important producers of natural products, which have played key roles in understanding biology and treating disease. However, the full potential of microbes to produce natural products has yet to be realized; the overwhelming majority of natural product gene clusters encoded in microbial genomes remain "cryptic", and have not been expressed or characterized. In contrast to the fast-growing number of genomic sequences and bioinformatic tools, methods to connect these genes to natural product molecules are still limited, creating a bottleneck in genome-mining efforts to discover novel natural products. Here we review developing technologies that leverage the power of homologous recombination to directly capture natural product gene clusters and express them in model hosts for isolation and structural characterization. Although direct capture is still in its early stages of development, it has been successfully utilized in several different classes of natural products. These early successes will be reviewed, and the methods will be compared and contrasted with existing traditional technologies. Lastly, we will discuss the opportunities for the development of direct capture in other organisms, and possibilities to integrate direct capture with emerging genome-editing techniques to accelerate future study of natural products.

摘要

微生物是天然产物的重要生产者,天然产物在理解生物学和治疗疾病方面发挥了关键作用。然而,微生物产生天然产物的全部潜力尚未实现;微生物基因组中编码的绝大多数天然产物基因簇仍然“沉默”,尚未得到表达或表征。与快速增长的基因组序列数量和生物信息学工具相比,将这些基因与天然产物分子联系起来的方法仍然有限,这在发现新型天然产物的基因组挖掘工作中形成了瓶颈。在这里,我们综述了一些正在发展的技术,这些技术利用同源重组的力量直接捕获天然产物基因簇,并在模式宿主中表达它们以进行分离和结构表征。尽管直接捕获仍处于早期发展阶段,但它已成功应用于几类不同的天然产物。我们将回顾这些早期成功案例,并将这些方法与现有的传统技术进行比较和对比。最后,我们将讨论在其他生物体中发展直接捕获的机会,以及将直接捕获与新兴的基因组编辑技术相结合以加速未来天然产物研究的可能性。

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