a Pharmaceutical Institute, Department of Pharmaceutical Biology , University of Tübingen , Tübingen , Germany.
b German Centre for Infection Research (DZIF), Partner Site Tübingen , Tübingen , Germany.
RNA Biol. 2017 Nov 2;14(11):1617-1626. doi: 10.1080/15476286.2017.1341020. Epub 2017 Jul 31.
FK506 (tacrolimus) is a valuable immunosuppressant produced by several Streptomyces strains. In the genome of the wild type producer Streptomyces tsukubaensis NRRL18488, FK506 biosynthesis is encoded by a gene cluster that spans 83.5 (kb). A whole transcriptome differential shotgun sequencing (dRNA-seq) of S. tsukubaensis was performed to analyze transcription at 2 different time points; before and during active FK506 production. In total, 8,914 transcription start sites were identified in either condition, which enabled precise determination of the 5'-UTR length of the corresponding transcripts as well as the identification of 2 consensus sequence motifs in the promoter regions. The transcription start sites of all gene operons within the FK506 cluster were identified, including 3 examples of leaderless RNA transcripts. These data provide detailed insight into the transcription of the FK506 biosynthetic gene cluster to support future regulatory studies, genetic manipulation, and industrial production.
FK506（他克莫司）是由几种链霉菌菌株产生的一种有价值的免疫抑制剂。在野生型产 FK506 的链霉菌株 Streptomyces tsukubaensis NRRL18488 的基因组中，FK506 生物合成由一个跨越 83.5 kb 的基因簇编码。对 S. tsukubaensis 进行了全转录组差异 shotgun 测序（dRNA-seq），以分析在 2 个不同时间点（开始和活跃的 FK506 生产期间）的转录情况。总共在两种条件下鉴定了 8914 个转录起始位点，这使得能够精确确定相应转录物的 5'-UTR 长度，以及在启动子区域中鉴定出 2 个保守序列基序。鉴定了 FK506 簇内所有基因操纵子的转录起始位点，包括 3 个无 leader RNA 转录本的例子。这些数据提供了对 FK506 生物合成基因簇转录的详细了解，以支持未来的调控研究、遗传操作和工业生产。
