Evolution and diversity of oxidoreductases involved in redox balance and energy conservation

The regulation of redox balance and energy conservation is fundamental to life and relies on a large evolutionary network of oxidoreductases forming homologous protein complexes, collectively termed HORBEC (homologous oxidoreductase complexes involved in redox balance and energy conservation). These include hydrogenases, respiratory complex I and electron-bifurcating complexes, central to respiration, fermentation and methanogenesis. Despite their crucial role, a comprehensive investigation of the diversity and evolutionary history of HORBEC has been lacking. Here we exhaustively identified and analysed over 50 protein families representing all HORBEC components across thousands of bacterial and archaeal genomes. We propose a unified nomenclature and classification encompassing 31 complexes and provide an annotation tool. We highlight the extensive diversity of HORBEC, especially in Archaea. We provide information on overlooked systems and identify a new one probably acting as a cation transport platform. We show that HORBEC originated via extensive tinkering of ancestral modules, driven by strong evolutionary constraints. Finally, we infer the presence of respiratory complex I in the last universal common ancestor, opening questions on its potential role in early energy metabolisms. This work provides an evolutionary framework for HORBEC, representing a fundamental resource to predict and study redox metabolisms of ecological and biotechnological significance.