Abstracts
GBM PhD Award
Structural basis of CO2 fixation and energy conservation in acetogens
Presenting author: Anuj Kumar
Authors: Anuj Kumar1, J. Roth2, H. Dietrich2, A. Katsyv2, F. Kremp2, S. Bohn3,
P. Saura4, H. Kim4, R.D. Righetto5, B.D. Engel5, V.R.I. Kaila4, V. Mü ller2, J. M. Schuller1
1- Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry, Philipps-University Marburg,
Marburg, Germany.
2 - Department of Molecular Microbiology & Bioenergetics, Institute of Molecular Biosciences, Johann Wolfgang
Goethe University, Frankfurt am Main, Germany.
3 - Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Munich, Germany.
4 - Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
5 - Biozentrum, University of Basel, Basel, Switzerland
Carbon dioxide (CO2) fixation and sequestration has gained significant attention due to the existential threat of climate change. Among exciting alternatives to capture and
fix CO2, biological CO2 reduction by acetogens stands apart. Acetogens are a phylogenetically diverse group of strictly anaerobic bacteria that fix CO2 while thriving
in extremely energy-limited environments. They convert two molecules of CO2 into a single molecule of acetyl-CoA via the Wood–Ljungdahl pathway (WLP); the only
known pathway that links CO2 fixation with two life-sustaining conditions: energy conservation and biomass production. Operating at the thermodynamic limits of life,
this pathway relies on highly efficient and exquisitely specific enzymes, making acetogens an ideal model to probe bioenergetic constraints and the potential
evolutionary origins of early metabolism. Despite biochemical and physiological characterization of the enzymes associated with WLP, structural insights into how
these bioenergetic machines function have remained open questions. In my thesis work, I employed redox-controlled single particle cryo-EM in combination with
biochemical and cryo-ET approaches, to gain a comprehensive understanding of these oxygen-sensitive metalloproteins. I could showcase that the molecular
principles of supercomplex assembly¹, modularity²˒³, and redox-driven conformational changes⁴ uncovered in this thesis are broadly conserved across anaerobic
organisms and thus are generalizable strategies underlying energy conservation and the chemically demanding reactions required to sustain life at the thermodynamic
limit.
References
(1) Dietrich, H.M.*, Righetto, R.D.*, Kumar, A. et al. Nature 607, 823–830 (2022).
(2) Katsyv, A.*, Kumar, A.*, Saura, P*. et al., JACS, 145 (10), 5696-5709 (2023).
(3) Kumar, A.*, Kremp, F.*, Roth, J. et al. Nat Commun 14, 5484 (2023).
(4) Kumar, A.*, Roth, J.*, Kim, H.* et al. Nat Commun 16, 2302 (2025).