1+1 = 3: a fusion of 2 enzymes in the methionine salvage pathway of Tetrahymena thermophila creates a trifunctional enzyme that catalyzes 3 steps in the pathway.
The methionine salvage pathway is responsible for regenerating methionine from its derivative, methylthioadenosine. The complete set of enzymes of the methionine pathway has been previously described in bacteria. Despite its importance, the pathway has only been fully described in one eukaryotic organism, yeast. Here we use a computational approach to identify the enzymes of the methionine salvage pathway in another eukaryote, Tetrahymena thermophila. In this organism, the pathway has two fused genes, MTNAK and MTNBD. Each of these fusions involves two different genes whose products catalyze two different single steps of the pathway in other organisms. One of the fusion proteins, mtnBD, is formed by enzymes that catalyze non-consecutive steps in the pathway, mtnB and mtnD. Interestingly the gene that codes for the intervening enzyme in the pathway, mtnC, is missing from the genome of Tetrahymena. We used complementation tests in yeast to show that the fusion of mtnB and mtnD from Tetrahymena is able to do in one step what yeast does in three, since it can rescue yeast knockouts of mtnB, mtnC, or mtnD. Fusion genes have proved to be very useful in aiding phylogenetic reconstructions and in the functional characterization of genes. Our results highlight another characteristic of fusion proteins, namely that these proteins can serve as biochemical shortcuts, allowing organisms to completely bypass steps in biochemical pathways.
Biology Department, Pomona College, Claremont, California, USA.
Hannah M W
HM
Salim
Maria Cristina
MC
Negritto
Andre R O
AR
Cavalcanti
D000818:Animals; D053898:Biosynthetic Pathways; D002384:Catalysis; D050939:Gene Fusion; D008715:Methionine / Q000096:biosynthesis*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D015800:Protozoan Proteins; D008715:Methionine