title: Genomic and transcriptomic insights into the thermo-regulated biosynthesis of validamycin in Streptomyces hygroscopicus 5008.
abstract: BACKGROUND
  Streptomyces hygroscopicus 5008 has been used for the production of the antifungal validamycin/jinggangmycin for more than 40 years. A high yield of validamycin is achieved by culturing the strain at 37°C, rather than at 30°C for normal growth and sporulation. The mechanism(s) of its thermo-regulated biosynthesis was largely unknown.
  
  
  RESULTS
  The 10,383,684-bp genome of strain 5008 was completely sequenced and composed of a linear chromosome, a 164.57-kb linear plasmid, and a 73.28-kb circular plasmid. Compared with other Streptomyces genomes, the chromosome of strain 5008 has a smaller core region and shorter terminal inverted repeats, encodes more α/β hydrolases, major facilitator superfamily transporters, and Mg2+/Mn2+-dependent regulatory phosphatases. Transcriptomic analysis revealed that the expression of 7.5% of coding sequences was increased at 37°C, including biosynthetic genes for validamycin and other three secondary metabolites. At 37°C, a glutamate dehydrogenase was transcriptionally up-regulated, and further proved its involvement in validamycin production by gene replacement. Moreover, efficient synthesis and utilization of intracellular glutamate were noticed in strain 5008 at 37°C, revealing glutamate as the nitrogen source for validamycin biosynthesis. Furthermore, a SARP-family regulatory gene with enhanced transcription at 37°C was identified and confirmed to be positively involved in the thermo-regulation of validamycin production by gene inactivation and transcriptional analysis.
  
  
  CONCLUSIONS
  Strain 5008 seemed to have evolved with specific genomic components to facilitate the thermo-regulated validamycin biosynthesis. The data obtained here will facilitate future studies for validamycin yield improvement and industrial bioprocess optimization.
authors: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Hang
authors: H
authors: Wu
authors: Shuang
authors: S
authors: Qu
authors: Chenyang
authors: C
authors: Lu
authors: Huajun
authors: H
authors: Zheng
authors: Xiufen
authors: X
authors: Zhou
authors: Linquan
authors: L
authors: Bai
authors: Zixin
authors: Z
authors: Deng
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D023281:Genomics / Q000379:methods*; D005971:Glutamates / Q000378:metabolism; D007294:Inositol / Q000031:analogs & derivatives / Q000096:biosynthesis; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D013696:Temperature; D059467:Transcriptome / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D005971:Glutamates; D007294:Inositol; C003749:validamycins; D002244:Carbon; D009584:Nitrogen