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A decade ago, a novel mechanism to drive thermodynamically unfavorable redox reactions was discovered that is used in prokaryotes to drive endergonic electron transfer reactions by a direct coupling to an exergonic redox reaction in one soluble enzyme complex. This process is referred to as flavin-based electron bifurcation, or FBEB. An important function of FBEB is that it allows the generation of reduced low-potential ferredoxin (Fdred) from comparably high-potential electron donors such as NADH or molecular hydrogen (H2). Fdred is then the electron donor for anaerobic respiratory chains leading to the synthesis of ATP. In many metabolic scenarios, Fd is reduced by metabolic oxidoreductases and Fdred then drives endergonic metabolic reactions such as H2 production by the reverse, electron confurcation. FBEB is energetically more economical than ATP hydrolysis or reverse electron transport as a driving force for endergonic redox reactions; thus, it does “save” cellular ATP. It is essential for autotrophic growth at the origin of life and also allows for heterotrophic growth on certain low-energy substrates.
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