Leibniz Institute for Natural Product Research and Infection Biology (HKI), Beutenbergstrasse 11a, 07745 Jena, Germany.
Nat Rev Microbiol. 2013 Jan;11(1):21-32. doi: 10.1038/nrmicro2916. Epub 2012 Nov 26.
Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.
真菌产生多种已知的低分子量化合物，被称为次生代谢产物，这些化合物在转录、发育和细胞间通讯等多种细胞过程中发挥作用。此外，其中许多化合物现在具有重要的应用价值，例如作为抗生素或免疫抑制剂。基因组挖掘工作表明，真菌产生次生代谢产物的能力被大大低估了，因为许多真菌次生代谢产物生物合成基因簇在标准培养条件下处于沉默状态。在这篇综述中，我描述了我们目前对调节参与次生代谢的基因转录的调控元件的理解。我还讨论了如何通过靶向激活沉默基因簇，最终更好地理解这些重要化合物的生理和生态功能，并为药物发现开辟新途径。
