The necessity of combining genomic and enzymatic data to infer metabolic function and pathways in the smallest bacteria: amino acid, purine and pyrimidine metabolism in Mollicutes.

Bacteria of the class Mollicutes have no cell wall. One species, Mycoplasma genitalium is the personification of the simplest form of independent cell-free life. Its small genome (580 kbp) is the smallest of any cell. Mollicutes have unique metabolic properties, perhaps because of their limited coding space and high mutability. Based on 16S rRNA analyses the Mollicutes Mycoplasma gallisepticum is thought to be the most mutable bacteria. Enzyme activities found in most Bacteria are absent from Mollicutes. The functions of apparently absent genes and enzymes can apparently be fulfilled by other genes and their expression products that have multiple capabilities. Because of these and other properties predictions of their metabolism based only on, e.g., either annotation, enzymatic assay, proteomic studies or structural analyses is problematic. To obtain a more confident appraisal of the functional capabilities of these simplest cells genomic and enzymatic data were combined to obtain a "metabolic consensus". The consensus is represented by a biochemical circuit for central metabolism involving purine and pyrimidine interconversions and their linkages to amino acid metabolism, glycolysis and the pentose phosphate pathway in three human Mollicutes pathogens: Mycoplasma pneumoniae, Mycoplasma genitalium and Ureaplasma urealyticum.