Nature Chemical Biology, Published online: 26 July 2024; doi:10.1038/s41589-024-01690-6An examination of metabolic changes during B cell differentiation reveals that germinal center B cells selectively upregulate methylenetetrahydrofolate dehydrogenase 2-mediated one-carbon metabolism, resulting in increased availability of nucleotide precursors and...

Nature Chemical Biology, Published online: 26 July 2024; doi:10.1038/s41589-024-01688-0β-Lactam antibiotics are detected by the sensor domain of BlaR in methicillin-resistant Staphylococcus aureus. A class of inhibitors has been developed that targets this sensor domain and prevents downstream activation of the antibiotic response pathway.

Nature Chemical Biology, Published online: 26 July 2024; doi:10.1038/s41589-024-01691-5RAS proteins, central drivers of cancer, appeared ‘undruggable’ for almost 30 years. Here we provide a personal perspective on the effort leading to our initial report of KRASG12C inhibitors in 2013, and the decade of discoveries that followed.

Nature Chemical Biology, Published online: 26 July 2024; doi:10.1038/s41589-024-01678-2A new study combines massively parallel assays, transcriptomics and biophysical modeling to provide a framework for analyzing the effects of compounds that modulate pre-mRNA splicing. The results lend important insights into the mechanisms of drug action and facilitate...

Nature Chemical Biology, Published online: 26 July 2024; doi:10.1038/s41589-024-01689-zZhu et al. found that cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. Phospholipid synthesis acts as an integrative defense mechanism to sense and combat oxidative stress.

Nature Chemical Biology, Published online: 25 July 2024; doi:10.1038/s41589-024-01701-6We combine RNA thermometer genetic switches, cell-free protein expression and synthetic cell design to create cell-sized systems that can initiate the synthesis of soluble proteins at defined temperatures. We show that when these switches are used to control the expression...