Project description:Citramalate is a chemical of potential industrial importance. Efficient fermentations have been developed using recombinant E. coli as the chassis. The experiments explore the transcriptional reprogramming that occurs upon induction of citramalate production.
Project description:Small molecules not only are convenient and useful for controlling cell fates, but also can provide better understanding of the molecular mechanisms of cell-fate transitions. Here, we identified that spleen tyrosine kinase (Syk) inhibitor R406 could significantly promote the early stage of mouse chemical reprogramming. Furthermore, R406 alleviated the Syk-calcineurin (Cn)-nuclear factor of activated T cells (NFAT) signaling cascade-mediated suppression of glycine, serine and threonine metabolic genes transcriptionally, which is previously unrecognized. In turn, R406 upregulated metabolites of glycine, serine and threonine metabolism and downstream transsulfuration cysteine biosynthesis pathway and cysteine metabolism. Subsequently, increased cellular hydrogen sulfide (H2S) after R406 treatment downregulated oxidative phosphorylation (OXPHOS) and reactive oxygen species (ROS), modulated redox homeostasis, and significantly enhanced chemical reprogramming. In sum, our studies have not only improved the chemical reprogramming technique, but also identified interesting molecular mechanisms of chemical-induced pluripotent reprogramming, which hold great potentials in regenerative medicine.
