title: A preliminary study of the mechanism of nitrate-stimulated remarkable increase of rifamycin production in Amycolatopsis mediterranei U32 by RNA-seq.
abstract: BACKGROUND
  Rifamycin is an important antibiotic for the treatment of infectious disease caused by Mycobacteria tuberculosis. It was found that in Amycolatopsis mediterranei U32, an industrial producer for rifamycin SV, supplementation of nitrate into the medium remarkably stimulated the yield of rifamycin SV. However, the molecular mechanism of this nitrate-mediated stimulation remains unknown.
  
  
  RESULTS
  In this study, RNA-sequencing (RNA-seq) technology was employed for investigation of the genome-wide differential gene expression in U32 cultured with or without nitrate supplementation. In the presence of nitrate, U32 maintained a high transcriptional level of genes both located in the rifamycin biosynthetic cluster and involved in the biosynthesis of rifamycin precursors, including 3-amino-5-dihydroxybenzoic acid, malonyl-CoA and (S)-methylmalonyl-CoA. However, when nitrate was omitted from the medium, the transcription of these genes declined sharply during the transition from the mid-logarithmic phase to the early stationary phase. With these understandings, one may easily propose that nitrate stimulates the rifamycin SV production through increasing both the precursors supply and the enzymes for rifamycin biosynthesis.
  
  
  CONCLUSIONS
  It is the first time to thoroughly illustrate the mechanism of the nitrate-mediated stimulation of rifamycin production at the transcriptional level, which may facilitate improvement of the industrial production of rifamycin SV, e.g. through optimizing the global rifamycin biosynthetic pathways on the basis of RNA-seq data.
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. zhshao@sibs.ac.cn.
authors.forename: Zhi Hui
authors.initials: ZH
authors.lastname: Shao
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. rensx@sina.com.cn.
authors.forename: Shuang Xi
authors.initials: SX
authors.lastname: Ren
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. 979531298@qq.com.
authors.forename: Xin Qiang
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China. joephy51@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. zzyanhan@126.com.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. gpzhao@sibs.ac.cn.|State Key Lab of Genetic Engineering and Center for Synthetic Biology, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 200032, China. gpzhao@sibs.ac.cn.|Shanghai-MOST Key Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, 201203, China. gpzhao@sibs.ac.cn.|Department of Microbiology and Li KaShing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Sar, China. gpzhao@sibs.ac.cn.
authors.forename: Guo Ping
authors.initials: GP
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 20032, China. jinwang@sibs.ac.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012294:Rifamycins; D059467:Transcriptome
chemical_list: D009566:Nitrates; D012294:Rifamycins; D012313:RNA; C023808:rifamycin SV