Fig. 5: Met4 and Met28 regulate different branches of sulphur metabolism in C. parapsilosis.

Sulphur-responsive genes based on the transcriptomic analysis, and their involvement in the import and assimilation of sulphur sources. All the genes written in black are upregulated in response to cysteine/methionine starvation in C. parapsilosis CLIB214. The expression of the genes in grey is not significantly affected by the absence of cysteine and methionine. The DEGs are boxed in coloured rectangles to incorporate information on how deleting MET4, MET28, or both affected the network that is controlled by these regulators (Supplementary Data 4 and Supplementary Table 2). The genes are boxed in blue if their expression is induced by Met28, and in pink if they are controlled by Met4 (Supplementary Data 4 and Supplementary Table 2). A split rectangle indicates that both regulators participate (see legend below the pathway). We could not determine if MET4 regulates itself because our data was obtained in a met4Δ strain: for this reason, half of the rectangle was left white. The pathway of inorganic sulphur assimilation into methionine (methyl cycle) and cysteine (transsulfuration pathway) through sequential reduction of sulphate into sulphite and then sulphide is conserved between C. parapsilosis and S. cerevisiae, but in C. parapsilosis the genes involved are mainly controlled by Met28. Met28 also controls the O-Acetyl-Serine (OAS) pathway (in green), which leads to the synthesis of cysteine from serine and sulphide and is absent in S. cerevisiae. On the contrary, Met4 is responsible for the expression of genes with a predicted role in the import and assimilation of organosulfur compounds (e.g., sulphate esters or sulfonates) (highlighted by the dotted-lined pink rectangle). The numbers in parenthesis indicate the presence of additional members of a gene family in the genome of C. parapsilosis, which are not overexpressed in the absence of Cys/Met in our dataset. The boxes representing the transporters are colour-coded based on their putative specificity for sulphate (teal), organosulfur compounds (green and yellow), or amino acids (purple). AdenoBisphos = adenosin 3’,5’-bisphosphate; THF = tetrahydrofolate.