dRNA-seq transcriptional profiling of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis NRRL18488 and general analysis of the transcriptome

RNA Biol. 2017 Nov 2;14(11):1617-1626. doi: 10.1080/15476286.2017.1341020. Epub 2017 Jul 31.

Abstract

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.

Keywords: FK506; Streptomyces; dRNA-seq; immunosuppressive; tacrolimus; transcription start sites; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • DNA, Bacterial / genetics*
  • DNA, Bacterial / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial*
  • Gene Library
  • Multigene Family
  • Operon
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Streptomyces / genetics*
  • Streptomyces / metabolism
  • Tacrolimus / metabolism*
  • Transcription Initiation Site
  • Transcriptome*

Substances

  • 5' Untranslated Regions
  • Bacterial Proteins
  • DNA, Bacterial
  • Tacrolimus