Nature Chemical Biology, Published online: 23 July 2024; doi:10.1038/s41589-024-01681-7 Soapwort (Saponaria officinalis) is a rich reservoir of triterpenoid glycosides that often have important pharmaceutical, nutraceutical and agronomical potential. Here, the authors elucidate the complete biosynthetic pathway of saponarioside B, a major saponin constituent in soapwort ..read more

Nature Chemical Biology, Published online: 22 July 2024; doi:10.1038/s41589-024-01685-3 Hybrids of macrolides and quinolones, called macrolones, can overcome macrolide-induced resistance through new interactions between the quinolone moiety and the ribosome and can concurrently inhibit both ribosome and DNA gyrase targets ..read more

Nature Chemical Biology, Published online: 22 July 2024; doi:10.1038/s41589-024-01683-5 SMAD ubiquitylation regulatory factor 1 (Smurf1) was identified as a critical activator of the phosphoinositide 3-kinase (PI3K)–Akt pathway by promoting phosphoinositide-dependent protein kinase 1 (PDK1) neddylation and cytoplasmic complex of PDK1 assembled with Smurf1 and SETDB1 (cCOMPASS) assembly. Smurf1-antagonizing repressor of tumor 1 (SMART1), a highly selective degrader for Smurf1, was developed and suppressed the tumor growth of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant colorectal ca ..read more

Nature Chemical Biology, Published online: 19 July 2024; doi:10.1038/s41589-024-01680-8 Using a combination of antibody- and LC–MS/MS-based methods, Zhang et al. reveal lysine l-lactylation as the key lactylation isomer in cellular histones, responding dynamically to glycolysis and positively correlating with lactyl-CoA levels, providing insights into the Warburg effect ..read more

Nature Chemical Biology, Published online: 19 July 2024; doi:10.1038/s41589-024-01679-1 This Perspective discusses the application of algorithmic methods throughout the preclinical phases of drug discovery to accelerate initial hit discovery, mechanism-of-action elucidation and chemical property optimization ..read more

Nature Chemical Biology, Published online: 15 July 2024; doi:10.1038/s41589-024-01672-8 Protein misfolding can spread from one molecule to another in infectious prion diseases. The propagation of protein misfolding has been directly observed in single protein molecules. These results showed that pathogenic mutants of the protein superoxide dismutase-1 (SOD1), which causes familial amyotrophic lateral sclerosis, imprint their misfolding onto native wild-type molecules ..read more

Nature Chemical Biology, Published online: 10 July 2024; doi:10.1038/s41589-024-01663-9 Biological reduction of dinitrogen by nitrogenase requires high-energy electrons to form ammonium ion. A new study reveals the structure and function of a molecular machine that exploits the proton-motive force to provide a powerful reductant used by the nitrogen-reducing system of the soil bacterium Azotobacter vinelandii ..read more

Nature Chemical Biology, Published online: 09 July 2024; doi:10.1038/s41589-024-01665-7 González-Delgado et al. developed retron-based editors termed multitrons, which can modify multiple sites on a single genome simultaneously. This technology is compatible with recombineering in prokaryotes and CRISPR editing in eukaryotes with applications in molecular recording, genome minimization and metabolic engineering ..read more

Nature Chemical Biology, Published online: 08 July 2024; doi:10.1038/s41589-024-01669-3 Through rational protein engineering and structure-guided ωRNA engineering, the ωRNA-guided endonuclease IscB system was developed into a highly efficient and compact genome-editing tool ..read more

Nature Chemical Biology, Published online: 08 July 2024; doi:10.1038/s41589-024-01659-5 The ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1) clustered regularly interspaced short palindromic repeats (CRISPR)–Cas system, which lacks the helical bundle domain in Cas8f, uses Cas1 to mediate the interference stage by connecting Cas2/3 to the DNA-bound CRISPR-associated complex for antiviral defense (Cascade ..read more