FANCY metabolomics

In the January Nature Biotechnology, Raamsdonk et al. find that, even when mutation of a gene causes no obvious phenotype, metabolite profiling can still give clues to gene function (Nat Biotechnol 2001, 19:45-50). Their test case involves two yeast strains deleted for either one of the two redundant genes for 6-phosphofructo-2-kinase (6-PF-2-K). These deletion strains fail to show a growth defect, even in chemostat competition experiments, but an analysis of specific metabolites clearly sets them apart from wild-type yeast. Raamsdonk et al. then test a more general method, in which the extracts from the two deletion strains and several other metabolic mutants are analyzed by 1H-NMR spectroscopy. Even without identifying the individual metabolites whose concentrations have changed, the two 6-PF-2-K mutants can be clustered together based on the similar changes in particular peaks. This method, dubbed functional analysis by co-responses in yeast (FANCY), is now being applied to a collection of yeast deletion mutants.