Metabolic response of a chemolithoautotrophic archaeon to carbon limitation

The ubiquitously distributed ammonia-oxidizing archaea generate energy from ammonia and build cell mass from inorganic carbon sources, thereby contributing to both the global nitrogen and carbon cycles. However, little is known about the regulation of their predicted core carbon metabolism. A thermodynamic model for Nitrososphaera viennensis was developed to estimate the consumption of inorganic carbon in relation to ammonia consumed for energy and was tested experimentally by growing cells in carbon-limited and excess conditions. A combined proteomic and metabolomic approach to the experimental conditions revealed distinct metabolic adaptation depending on the amount of carbon supplied, either in a catalase or pyruvate background as a reactive oxygen species scavenger. Integration of protein and metabolite dynamics revealed a cellular strategy under carbon limitation to maintain a pool of amino acids and an upregulation of proteins necessary for translation initiation to stay primed for protein synthesis. The combination of modeling and functional genomics fills gaps in the understanding of the central metabolism and its regulation in a chemolithoautotrophic, ammonia-oxidizing archaeon, even in the absence of available genetic tools.IMPORTANCELittle is known about the regulation of carbon metabolism within ammonia-oxidizing archaea (AOA), a widespread clade that plays a critical role in the global nitrogen cycle while also fixing inorganic carbon. To address this missing knowledge, the soil AOA Nitrososphaera viennensis was subjected to various levels of inorganic carbon and analyzed via a systems biology approach to better understand how its core metabolism is regulated. The results demonstrate a strong dependence on the carbon fixation cycle and highlight key connection points between the core metabolic pathways. The analysis additionally revealed tight control on translational processes and elucidated unique cellular responses when the organism was exposed to either exogenous catalase or pyruvate to relieve oxidative stress from reactive oxygen species. The presented data highlight metabolic responses of N. viennensis and provide a better understanding of how the organism, and likely other AOA, respond to various environmental conditions.