Modulation of the complex regulatory network for methionine biosynthesis in fungi

In this study, C. albicans regulates its methionine biosynthetic pathways using the transcription factors Met4 and Cbf1. This circuitry appears more complex than that of filamentous fungi, which use orthologs of the Met4 transcription factor, but lack versions of Cbf1, but is considerably less complex than that of S. cerevisiae, which 2 requires two transcription complexes, involving Cbf1 and Met31/32 as DNA binding modules, and Met4 and the Met4 ortholog Met28 as co-activators, to regulate Met biosynthesis. Although C. albicans contains Met31/32 and Met28 orthologs, they do not appear to be linked to regulation of the methionine circuit. Thus, the phylogenetic progression from filamentous fungi to S. cerevisiae is characterized by increasing complexity of the regulators, although the structural elements of the pathways are fundamentally the same. Liquid cultures of all strains were adjusted to OD600 at 0.8 in 10 mL liquid YPD medium and incubated at 30 degrees with shaking at 220 rpm. We conduted RNAseq profiling for 2 replicates.

本研究中，白色念珠菌(C. albicans)通过转录因子Met4与Cbf1调控其甲硫氨酸生物合成通路。该调控回路的复杂程度高于丝状真菌——丝状真菌仅拥有Met4转录因子的同源基因，却缺失Cbf1的同源蛋白，但又远低于酿酒酵母(S. cerevisiae)的调控体系：酿酒酵母需要两套转录复合物来调控甲硫氨酸合成，其中Cbf1与Met31/32作为DNA结合模块，Met4及其同源蛋白Met28作为共激活因子。尽管白色念珠菌也携带Met31/32与Met28的同源基因，但二者似乎并未参与甲硫氨酸代谢通路的调控。综上，从丝状真菌到酿酒酵母的演化进程中，甲硫氨酸合成通路的调控因子复杂度逐步提升，尽管该通路的结构元件本质上并无差异。本研究将所有菌株的液体培养物调整至OD600为0.8，接种于10 mL YPD液体培养基中，于30℃、220 rpm振荡培养。我们对两份生物学重复样本进行了RNA测序(RNA-seq)分析。