Premium
Mycothiol regulates and is regulated by a thiol‐specific antisigma factor RsrA and σ R in Streptomyces coelicolor
Author(s) -
Park JooHong,
Roe JungHye
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06191.x
Subject(s) - streptomyces coelicolor , biology , regulon , biochemistry , cysteine , thiol , glutathione , intracellular , transcription factor , mutant , sigma factor , gene , streptomyces , gene expression , promoter , genetics , bacteria , enzyme
Summary Mycothiol (MSH) is a small thiol molecule with a cysteine‐ligated disaccharide structure found in actinomycetes that include streptomycetes and mycobacteria. In Streptomyces coelicolor , a model organism for antibiotic production and differentiation, the amount of MSH is under the control of a sigma factor σ R , which is regulated by an antisigma factor RsrA with a thiol‐disulphide redox switch. We found that the first gene ( mshA ) in the biosynthetic pathway for MSH and the gene for amidase ( mca ) that participates in detoxifying mycothiol‐reactive drugs are under direct control of σ R . The σ R target genes are induced not only by a thiol oxidant diamide, but also by alkylating agents that cause a rapid decrease in MSH. Expression of the σ R regulon was also elevated in MSH‐deficient mutants, suggesting that a decrease in the level of MSH is a natural intracellular trigger for σ R activation. We found that MSH was capable of reducing RsrA to bind σ R , whereas glutathione was not. These results support a proposal that the RsrA‐σ R system senses the intracellular level of reduced MSH, and that MSH serves as a natural modulator of the transcription system for its own replenishment in addition to being a redox buffer and drug detoxifier.