An important and largely unanswered question in biology is how the cell integrates the large number of metabolic pathways that comprise its intermediary metabolism. The wealth of genomic information and new technologies developed in recent years make this exciting area of metabolism accessible to researchers. In the last four years, work in the PI's laboratory uncovered a pathway previously thought to be unique to eucaryotes for propionate catabolism in S. enterica and other procaryotes. Although substantial progress has been made toward a better understanding of the biochemistry of this pathway, gaps in our knowledge remain. Studies of regulation of expression of the genes encoding propionate-degrading enzymes identified an interaction between this pathway and the pathway for the degradation of 1,2-propanediol. The well-characterized genetic system of S. enterica offers a unique opportunity to dissect the molecular details of the metabolic integration of these two pathways. Interest in learning more about this example of metabolic pathway integration was increased by the involvement of a protein of S. enterica (CobB) for which there are orthologues in bacteria, archaea, and eucaryotes, including humans. In eucaryotes, CobB orthologues comprise the family of SIR2 regulatory proteins that are involved in the complex process of gene splicing. It has been demonstrated that the human SIR2 protein can compensate for the lack of the CobB protein during cell growth on propionate. The study of CobB function presents a worthwhile opportunity to learn about metabolic integration and other strategies that ensure proper cell function.
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