Metagenomics-guided analysis of microbial chemolithoautotrophic phosphite oxidation yields evidence of a seventh natural CO 2 fixation pathway

Significance Phosphite (HPO 3 2− ) is the most energetically favorable biological electron donor known, but only one organism capable of growing by phosphite oxidation has been previously identified. Here, we describe a phosphite-oxidizing bacterium that can grow with CO 2 as its sole electron acceptor, and we propose a metabolic model in which inorganic carbon is assimilated via the reductive glycine pathway. Although the reductive glycine pathway has previously been identified as a “synthetic” carbon fixation pathway, this study provides evidence that it may actually function as a natural autotrophic pathway. Our results suggest that phosphite may serve as a driver of microbial growth and carbon fixation in energy-limited environments, particularly in aphotic environments lacking alternative terminal electron acceptors.