SurR is a master regulator of the primary electron flow pathways in the order Thermococcales

The sulfur response regulator, SurR, is among a handful of known redox-active transcriptional regulators. First characterized from the hyperthermophile Pyrococcus furiosus, it is unique to the archaeal order Thermococcales. P. furiosus has two modes of electron disposal. Hydrogen gas is produced when the organism is grown in the absence of elemental sulfur (S⁰ ) and H₂ S is produced when grown in its presence. Switching between these metabolic modes requires a rapid transcriptional response and this is orchestrated by SurR. We show here that deletion of SurR causes severely impaired growth in the absence of S⁰ since genes essential for H₂ metabolism are no longer activated. Conversely, a strain containing a constitutively active SurR variant displays a growth phenotype in the presence of S⁰ due to constitutive repression of S⁰ -responsive genes. During a metabolic shift initiated by addition of S⁰ to the growth medium, both strains demonstrate a de-regulation of genes involved in the SurR regulon, including hydrogenase and related S⁰ -responsive genes. These results demonstrate that SurR is a master regulator of electron flow within P. furiosus, likely affecting the pools of ferredoxin, NADPH and NADH, as well as influencing metabolic pathways and thiol/disulfide redox balance.