Thiosulfate dehydrogenase: an unusual acidophilic c-type cytochrome

• Applicant: Privatdozentin Dr. Christiane Dahl
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198187081

Evidence is emerging that c-type cytochromes with an unusual axial histidine-cysteine coordination of the heme iron play a pivotal role in sulfur-based energy metabolism. The diheme cytochrome c TsdA that acts as thiosulfate dehydrogenase or tetrathionate reductase in vivo depending on the host organism and growth conditions, was recently identified as another member of this exciting group of proteins. Although wide spread not only in Proteobacteria but also in other bacterial phyla, detailed knowledge about the reaction mechanism, the biophysical and structural properties as well as the exact physiological role of TsdA is not available. This project is intended to fill this gap by focussing on two prototypes of the enzyme: [1] Thiosulfate dehydrogenase from the purple sulfur bacterium Allochromatium vinosum that does not only carry one heme with unusual axial His/Cys coordination but a second heme exhibiting an unprecedented switch of a His/Lys to His/Met ligation of heme 2 upon reduction. [2] The bifunctional tetrathionate reductase/thiosulfate dehydrogenase from the human gut pathogen Campylobacter jejuni. This enzyme appears to be especially adapted to catalyzing tetrathionate reduction. Structural comparisons indicate missing/different axial ligation of one heme group as one factor contributing to the different properties of these two TsdA prototypes. Molecular genetic work with the source organisms and tsdA null as well as complementation mutants in combination with detailed biophysical, electrochemical and structural characterization and comparison of the two TsdA prototypes will answer the following questions[1] Which are the molecular details that underlie the adaptation of TsdA proteins to function preferentially either in thiosulfate oxidation or tetrathionate reduction?[2] Which are the physiological functions and advantages of thiosulfate dehydrogenase/tetrathionate reductase? Answers to these questions will contribute to a thorough understanding of this novel and unusual type of cytochromes. Furthermore, the results of this project will shed light on the relevance of thiosulfate not only in bacteria dedicated to energy-generating sulfur metabolism but also in thiosulfate/tetrathionate metabolizing organoheterotrophs relevant to human health.

• DFG Programme: Research Grants