FNR-Type Regulator GoxR of the Obligatorily Aerobic Acetic Acid Bacterium Affects Expression of Genes Involved in Respiration and Redox Metabolism.

Gene expression in the obligately aerobic acetic acid bacterium responds to oxygen limitation, but the regulators involved are unknown. In this study, we analyzed a transcriptional regulator named GoxR (GOX0974), which is the only member of the fumarate-nitrate reduction regulator (FNR) family in this species. Evidence that GoxR contains an iron-sulfur cluster was obtained, suggesting that GoxR functions as an oxygen sensor similar to FNR. The direct target genes of GoxR were determined by combining several approaches, including a transcriptome comparison of a Δ mutant with the wild-type strain and detection of GoxR binding sites by chromatin affinity purification and sequencing (ChAP-Seq). Prominent targets were the genes encoding a cytochrome oxidase with low O affinity, which were repressed by GoxR, and the operon, which was activated by GoxR. The operon encodes a transhydrogenase (), an NADH-dependent oxidoreductase (GOX0313), and another oxidoreductase (GOX0314). Evidence was obtained for GoxR being active despite a high dissolved oxygen concentration in the medium. We suggest a model in which the very high respiration rates of due to periplasmic oxidations cause an oxygen-limited cytoplasm and insufficient reoxidation of NAD(P)H in the respiratory chain, leading to inhibited cytoplasmic carbohydrate degradation. GoxR-triggered induction of the operon enhances fast interconversion of NADPH and NADH by the transhydrogenase and NADH reoxidation by the GOX0313 oxidoreductase via reduction of acetaldehyde formed by pyruvate decarboxylase to ethanol. In fact, small amounts of ethanol were formed by under oxygen-restricted conditions in a GoxR-dependent manner. serves as a cell factory for oxidative biotransformations based on membrane-bound dehydrogenases and as a model organism for elucidating the metabolism of acetic acid bacteria. Surprisingly, to our knowledge none of the more than 100 transcriptional regulators encoded in the genome of has been studied experimentally until now. In this work, we analyzed the function of a regulator named GoxR, which belongs to the FNR family. Members of this family serve as oxygen sensors by means of an oxygen-sensitive [4Fe-4S] cluster and typically regulate genes important for growth under anoxic conditions by anaerobic respiration or fermentation. Because has an obligatory aerobic respiratory mode of energy metabolism, it was tempting to elucidate the target genes regulated by GoxR. Our results show that GoxR affects the expression of genes that support the interconversion of NADPH and NADH and the NADH reoxidation by reduction of acetaldehyde to ethanol.

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