Functional expression of SCO7832 stimulates tautomycetin production via pathway-specific regulatory gene overexpression in Streptomyces sp. CK4412

J Ind Microbiol Biotechnol. 2009 Jul;36(7):993-8. doi: 10.1007/s10295-009-0580-5. Epub 2009 May 1.

Abstract

Comparative transcriptome analysis has revealed several acidic pH shock-induced genes presumably involved with stimulation of antibiotic production by S. coelicolor (Kim et al. Appl Microbiol Biotechnol 2007). Streptomyces sp. CK4412 produces a novel T cell-specific immunosuppressive compound, tautomycetin (TMC). When cultured at acidic pH medium, it also exhibited higher TMC productivity. To verify a gene responsible for acidic pH shock-induced TMC stimulation, a putative acid-shock-induced gene, SCO7832 encoding an Na(+)/H(+) antiporter protein, was cloned under the influence of a strong constitutive ermE* promoter in an integrative expression pSET152 vector. This was followed by its conjugation into the TMC-producing Streptomyces sp. CK4412. Comparing TMC production and antifungal activity of wild-type and the SCO7832-containing exconjugant revealed that SCO7832 stimulated TMC production more than 3.5-fold in Streptomyces sp. CK4412. The over-expression of SCO7832 did not affect the ratio between intra- and extra-cellular TMC productions. However, it significantly stimulated the expression of a TMC-specific positive regulatory gene. This implies that the stimulatory effect of SCO7832 functions in TMC-producing Streptomyces sp. CK4412 via up-regulation of a TMC pathway-specific positive regulatory gene, tmcN overexpression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Biosynthetic Pathways / genetics*
  • Furans
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Gene Expression*
  • Genes, Bacterial
  • Genetic Engineering
  • Lipids / biosynthesis*
  • Recombination, Genetic
  • Streptomyces coelicolor / genetics*
  • Streptomyces coelicolor / metabolism*
  • Stress, Physiological

Substances

  • Acids
  • Anti-Bacterial Agents
  • Furans
  • Lipids
  • tautomycetin