Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University Campus, Building E8 1, 66123 Saarbrücken, Germany.
Nat Prod Rep. 2016 Aug 27;33(8):1006-19. doi: 10.1039/c6np00002a. Epub 2016 Jul 20.
Covers the period up to 2016Bacterial-based natural products have long represented a promising resource for the development of commercially relevant therapeutics, and more than two thirds of these products have been developed from members of the genus Streptomyces. The extensive sequencing of bacterial genomes suggests that the majority of gene clusters encoding natural products are silent and not expressed under standard laboratory conditions. However, these clusters can be activated through systematic exchanges between native transcriptionally silent promoters and transcriptionally active promoters. Therefore, the availability of well-studied constitutive and inducible promoters is of the utmost importance for identifying natural products encoded by silent gene clusters. This manuscript provides an overview of the promoter control elements for streptomycetes and examples of their successful application in refactoring the biosynthetic pathways of natural products.
涵盖了截至 2016 年的时期。基于细菌的天然产物长期以来一直是开发具有商业相关性的治疗药物的有前途的资源,其中超过三分之二的这些产品是从链霉菌属的成员中开发出来的。细菌基因组的广泛测序表明,编码天然产物的大多数基因簇是沉默的,在标准实验室条件下不表达。然而,这些簇可以通过在天然转录沉默启动子和转录活性启动子之间进行系统交换来激活。因此,可利用的研究良好的组成型和诱导型启动子对于鉴定由沉默基因簇编码的天然产物至关重要。本文概述了链霉菌的启动子控制元件及其在重构天然产物生物合成途径方面的成功应用实例。