In recent decades, a number of hypotheses on the autotrophic origin of life have been presented. These proposals invoke the emergence of reaction networks leading from CO or CO2 to the organic molecules required for life. It has also been suggested that the last (universal) common ancestor (LCA or LUCA) of all extant cell lineages was a chemolitho-autotrophic thermophilic anaerobe. The antiquity of some carbon fixation pathways, the phylogenetic basal distribution of some autotrophic organisms, and the catalytic properties of iron-sulfur minerals have been advanced in support of these ideas. Here we critically examine the phylogenetic distribution and evolution of enzymes that are essential for two of the most ancient autotrophic means of metabolism: the reductive tricarboxylic acid (rTCA) cycle and the reductive acetyl-CoA pathway. Phylogenetic analysis of citryl-CoA synthetase and of citryl-CoA lyase, key enzymatic components of the rTCA cycle, and of CO dehydrogenase/acetyl-CoA synthase, a key enzyme in the reductive acetyl-CoA pathway, revealed that all three enzymes have undergone major lateral transfer events and therefore cannot be used as proof of the LCA’s metabolic abilities nor as evidence of an autotrophic origin of life. [Int Microbiol 2014; 17(2):91-97]

Keywords: autotrophic pathways · reverse Krebs cycle · Wood–Ljungdahl pathway · origin of life · last common ancestor (LCA, LUCA)