Transcriptional rewiring of fungal galactose-metabolism circuitry

Background: The Leloir-pathway genes encode the enzymatic machinery involved in the metabolism of galactose. Results: In the distantly related fungi Saccharomyces cerevisiae and Candida albicans, the genes encoding these enzymes are syntenically arranged, but the upstream regulatory regions are highly divergent. In S. cerevisiae, the Leloir-pathway genes are positively regulated by Gal4p acting through the UAS(G) sequence CGG(N-11)CCG. However, in C. albicans, the Gal4p and UAS(G) combination is found to regulate genes unrelated to galactose metabolism. We identified a palindromic sequence that acts to control GAL10 expression in C. albicans in the presence of galactose. This palindrome is found upstream of other Leloir-pathway genes in C. albicans, and in the absence of other regulatory sequences, activation of expression through this sequence in the presence of galactose requires Cph1p, the homolog of the Ste12p transcription factor of S. cerevisiae. Conclusions: Although the cellular process of galactose induction of the Leloir pathway is conserved between the two organisms, the regulatory circuits achieving the cellular process are completely distinct.