FIGURE 1.

The ETH bio-activation paradigm. ETH is activated by the monooxygenase EthA into its activated form, ETH^∗. The expression of EthA is regulated by the transcriptional repressor EthR, and both ethA and ethR are organized in a divergent operon with a shared intergenic promoter region. EthR dimers bind cooperatively as a homo-octamer to the specific operator in the ethA-ethR intergenic promoter region, repressing both ethA and ethR expression. The mycobacterial serine/threonine protein kinase PknF negatively regulates the physical binding of EthR to the DNA via phosphorylation of the EthR homo-octamer, hence promoting ethA-ethR expression. Additionally, the mycothiol synthesis pathway and its end product, mycothiol, have been implicated in ETH bio-activation as well.