Project 6 Prof. Thorsten Friedrich
Divergent evolution of nucleotide oxidation
The main focus of the project is on the comprehension of the similarities and differences of substrate oxidation by complex I from bacteria and archaea using structural and functional studies. Complex I in bacteria and eukaryotes couples the electron transfer from NADH to quinone with the translocation of protons across the membrane contributing to the proton-motive force that is essential for energy-consuming processes. Reactive oxygen species (ROS) are by-products of the NADH oxidation. Due to structural and functional studies a redox-gated mechanism for NADH oxidation to minimize ROS production was proposed.
As adaption to the different lifestyle, the complex in methanogenic archaea oxidizes F420H2 by the F420H2 dehydrogenase module. This module is not related to the bacterial NADH dehydrogenase module and evolved under anoxic conditions (Figure). However, both modules use a flavin mononucleotide and two iron-sulfur clusters for substrate oxidation. Nature’s strategy of preventing the formation of deleterious ROS during NADH oxidation will be elucidated by comparing the mechanism of the NADH oxidation in bacterial complex I with that of F420H2 oxidation by the archaeal F420H2 dehydrogenase complex.
Contact
Prof. Dr. Thorsten Friedrich
Dean of Studies of Chemistry
Institute of Biochemistry
Albertstr. 21
79104 Freiburg
Phone: +49 (0) 761 203-6060
Fax:+49 (0) 761 203-6096
email: thorsten.friedrich@uni-freiburg.de