Aims: To learn from life's past, mechanisms of resilience that can help us adapt new solutions for energy, water and agricultural productivity.
Premise: Life now occupies essentially every imaginable niche on earth, often defying our expectations of what is 'liveable'. Yet all known life requires fixed nitrogen in core molecular components and iron clusters are understood to have catalyzed biological reactions even before the systems would have been recognized as organisms.
Methods: We are combining the experimental study of non-Fe replacements for iron-dependent enzymes and electron carriers, to learn what other cofactors can be entrained to execute the same functions, and how. Our principal study systems have been the superoxide dismutases, representing non-heme iron centers. We are also studying biology's surrogates for one of the primordial catalysts, Fe4S4 clusters. 'Ironically', life has entrained organic cofactors for some of their roles. Particular emphasis has been placed on electronic structure and redox tuning. We complement these with phylogenetic analyses, to investigate recruitment of alternative catalytic modes to replace Fe-dependent ones.
Results: Proteins achieve remarkable re-tuning of bound redox cofactors, over ranges approaching 1 V.1 This results from a combination of multiple weaker interactions, in particular redox-coupled protons and conformational adjustments that are orchestrated by the larger structure of the protein.
Conclusions: Together, our studies reveal 'life' as a dynamic multi-dimensional process where the whole is much more resilient than the sum of the parts. However, the adaptations remain incompletely understood, and an ongoing source of challenging insights.
(1) Miller, A.-F. (2008) Redox tuning over almost 1 V in a structurally-conserved active site: lessons from Fe-containing superoxide dismutase, Acc. Chem. Res. 41, 501-510.