Comparative analysis of genome‐scale metabolic models for Mycoplasma genitalium, Ureaplasma parvum, and Mycoplasma hominis reveals novel routes through the Pentose Phosphate Pathway

Abstract

We have recently developed a high‐throughput computational pipeline for generating genome‐scale metabolic models. To test this pipeline, we have generated models for three mollicutes: Mycoplasma genitalium G‐37 (Mg), Ureaplasma parvum serovar 3 (Up), and Mycoplasma hominis (Mh). All three genomes lack an annotated transaldolase (TAL) gene, resulting in incomplete pentose phosphate pathways (PPP). However, all three organisms require production of phospho‐ribose‐diphosphate (PRPP), a key product of the PPP. To meet this demand, all three models predict novel routes through the PPP. The route predicted in the Mg and Up models relies on secondary activities of the phosphofructokinase (PFK) and fructose‐bisphosphate aldolase (FBA) enzymes to cope with the accumulation of sedoheptulose 7‐phosphate. This PPP bypass was recently discovered in an E. coli mutant lacking the TAL gene. Because Mh lacks a gene for PFK, the Mh model predicts a different route, reversing the activity of FBA and postulating the presence of Sedoheptulose‐1,7‐bisphosphatase. There is no genomic evidence for the presence of known forms of this enzyme in Mh; in this case, the model reveals the necessity of clarifying the pathway of PRPP production in Mh. Our study highlights the potential for comparative analysis of metabolic models to predict novel biochemistry and suggest testable hypotheses in prokaryotic metabolism.NSF MCB 0745100