Evolutionary roots of the citric acid cycle in prokaryotes

Advances in biochemistry, microbiology, and molecular biology suggest new approaches for exploring the early evolution of bioenergetic systems. These approaches, still in their infancy, are necessarily directed to detection of 'molecular fossils' in diverse extant prokaryotes. Since the Earth was devoid of atmospheric oxygen during early cellular evolution, it is likely that 'precursor fragments' of the classical citric acid cycle are to be found in contemporary anaerobic bacteria. Accumulating evidence indicates that such fragments originally served biosynthetic roles of one kind or another, before they were recruited for assembly of the energy-yielding aerobic cycle. The extraordinary versatility of citric acid cycle intermediates and reactions for multiple uses raises the possibility that origination of the aerobic cycle, viewed as an evolutionary event, occurred more than once.