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

Abstract

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 (S ) and H 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 S since genes essential for H metabolism are no longer activated. Conversely, a strain containing a constitutively active SurR variant displays a growth phenotype in the presence of S due to constitutive repression of S -responsive genes. During a metabolic shift initiated by addition of S to the growth medium, both strains demonstrate a de-regulation of genes involved in the SurR regulon, including hydrogenase and related S -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.

Conserved principles of transcriptional networks controlling metabolic flexibility in archaea

“…When S 0 is present in the environment, a CXXC motif within SurR is oxidized, and SurR undergoes a redox switch that changes its conformation and disrupts SurR-DNA binding [20]. Repression of S 0 reduction genes is relieved, and H 2 S production proceeds [21]. This experimental evidence is summarized in Figure 3D.…”

“…Finally, we highlight two recently discovered archaeal TMnet examples. We describe the mechanisms underlying metabolic control and, for the first time, model the dynamical properties of the TMnet that regulates sulfur reduction in a thermophilic archaeal model species [20,21]. Using these examples, we argue that characterization and dynamical modeling of TMnets pinpoint knowledge gaps, laying the groundwork toward unifying properties of how metabolic flexibility is regulated.…”

“…When elemental S is absent, SurR binds to a GTT-n3-AAC motif, activating expression of its own gene and genes whose products are involved in hydrogen production (e.g. all three hydrogenases SI, SII, and [NiFe]-hydrogenase MBH) [21,66]. Under these conditions, SurR also represses genes encoding enzymes required for the reduction in elemental sulfur to H 2 S (e.g.…”

“…Under these conditions, SurR also represses genes encoding enzymes required for the reduction in elemental sulfur to H 2 S (e.g. protein disulfide oxidoreductase, sulfur reductase) [21,66]. When S 0 is present in the environment, a CXXC motif within SurR is oxidized, and SurR undergoes a redox switch that changes its conformation and disrupts SurR-DNA binding [20].…”

Two functionally distinct NADP+-dependent ferredoxin oxidoreductases maintain the primary redox balance of Pyrococcus furiosus

“…The second Nfn homolog of P. furiosus, termed NfnII (PF1910- 11), has yet to be structurally and functionally characterized and is the subject of this study. Interestingly, the expression of NfnI and NfnII are dependent upon sulfur availability and carbon source in a reciprocal fashion (10,11). Specifically, expression of nfnI is up-regulated under H 2 -producing conditions (sugar fermentation), whereas nfnII is up-regulated under S 0 -reducing conditions (with sugars or peptides as the carbon source).…”