M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):415-431. doi: 10.1007/s10295-018-2097-2. Epub 2018 Nov 16.
Actinomycetes produce many of the drugs essential for human and animal health as well as crop protection. Genome sequencing projects launched over the past two decades reveal dozens of cryptic natural product biosynthetic gene clusters in each actinomycete genome that are not expressed under regular laboratory conditions. This so-called 'chemical dark matter' represents a potentially rich untapped resource for drug discovery in the genomic era. Through improved understanding of natural product biosynthetic logic coupled with the development of bioinformatic and genetic tools, we are increasingly able to access this 'dark matter' using a wide variety of strategies with downstream potential application in drug development. In this review, we discuss recent research progress in the field of cloning of natural product biosynthetic gene clusters and their heterologous expression in validating the potential of this methodology to drive next-generation drug discovery.
放线菌产生了许多对人类和动物健康以及农作物保护至关重要的药物。在过去的二十年中，启动的基因组测序项目揭示了每个放线菌基因组中数十个隐藏的天然产物生物合成基因簇，这些基因簇在常规实验室条件下不表达。这种所谓的“化学暗物质”代表了基因组时代药物发现的一个潜在丰富的未开发资源。通过对天然产物生物合成逻辑的深入了解，以及生物信息学和遗传工具的发展，我们越来越能够使用各种策略来利用这种“暗物质”，这些策略在药物开发的下游具有潜在的应用。在这篇综述中，我们讨论了天然产物生物合成基因簇克隆及其在验证该方法在推动下一代药物发现方面的潜力方面的最新研究进展。
