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  • 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.

    • Seohyun Jo
    • Amr El-Demerdash
    • Anne Osbourn
    ArticleOpen Access
  • 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 cancer.

    • Zhiqiang Peng
    • Wei Fang
    • Lingqiang Zhang
    Article
  • The field of engineered living materials (ELMs) involves incorporating cells into materials to enable new functionalities. Now, ELMs have been developed that facilitate inter-kingdom communication between bacteria and eukaryotic cells using transcriptional regulation and extracellular electron transfer.

    • Joshua T. Atkinson
    News & Views
  • 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.

    • Denise B. Catacutan
    • Jeremie Alexander
    • Jonathan M. Stokes
    Perspective
  • 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.

    • Di Zhang
    • Jinjun Gao
    • Yingming Zhao
    ArticleOpen Access
  • 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.

    • Krishna Neupane
    • Abhishek Narayan
    • Michael T. Woodside
    Article
  • 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.

    • Günter Fritz
    • Peter M. H. Kroneck
    • Julia Steuber
    News & Views
  • 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.

    • Alejandro González-Delgado
    • Santiago C. Lopez
    • Seth L. Shipman
    Article
  • Time-resolved synthesis of target proteins via proximity-triggered protein trans-splicing has now been shown to enable the activation of a diverse set of proteins upon the addition or removal of control elements. This temporal precision allows for monitoring distinct phases in cellular signaling and unveiling the molecular connections of oncofusion kinases, including DNAJ–PKAc.

    • Gihoon Lee
    • Tom W. Muir
    Article
  • 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).

    • Laixing Zhang
    • Hao Wang
    • Yue Feng
    Article
  • Yan and Tang developed a CRISPR-based RNA-editing approach called DECOR by fusing a Cas13 variant to an evolved E. coli tRNA adenosine deaminase, TadA8e, enabling adenosine-to-inosine editing to specified sites in the human transcriptome.

    • Hao Yan
    • Weixin Tang
    Article
  • RNA-based genetic regulation has been used to control protein translation in synthetic cells in response to the external temperature. RNA thermometers enable in situ protein expression above permissive temperatures. Controlled expression of the membrane pore α-hemolysin allows small-molecule cargo to be released in a temperature-dependent manner.

    • Carolina Monck
    • Yuval Elani
    • Francesca Ceroni
    ArticleOpen Access
  • A major bottleneck of targeted protein degradation (TPD) has been the discovery of E3 ligases that are amenable to this strategy. Two new studies highlight the potential of FBXO22 as a candidate for TPD, thus expanding the toolbox of hijackable ligases.

    • Cyrus Jin
    • Milka Kostic
    News & Views
  • Lee, Barone et al. engineered a mutant form of LSD1, Y391K, which renders the nucleosome demethylase activity of LSD1 insensitive to Lys14 acetylation of histone H3, providing a useful tool to illuminate the functional consequences of disconnecting histone modification crosstalk.

    • Kwangwoon Lee
    • Marco Barone
    • Philip A. Cole
    Article
  • Basu et al. report a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen method for the discovery of E3 ligases suitable for targeted protein degradation and identify the E3 ligase F-box protein 22 capable of promoting ligand-induced degradation of multiple proteins.

    • Ananya A. Basu
    • Chenlu Zhang
    • Xiaoyu Zhang
    Article
  • Nie et al. describe a mechanism underlying the degradation of the histone methyltransferase NSD2 through the recruitment of FBXO22 E3 ligase, providing a chemical probe for NSD2 function study and targeted protein degradation.

    • David Y. Nie
    • John R. Tabor
    • Cheryl H. Arrowsmith
    Article