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  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peptides are fundamental in life and are widely used as therapeutic agents; however, they are problematic to produce by chemical synthesis. The discovery of unusual biosynthetic pathways that produce peptide natural products reveals an alternative approach for peptide synthesis that uses ‘standalone’ ligase enzymes rather than multimodular enzymes.

    Research Briefing
  • Total in vitro biosynthesis can reveal unusual pathways evolved by nature to produce natural products. Here the authors report on enzymatic cascades, comprising a cryptic methylation sequence, efficiently delivering β-lactone-containing peptide proteasome inhibitors with promising anticancer activity.

    • Guangcai Xu
    • Daniele Torri
    • Jason Micklefield
    ArticleOpen Access
  • The enzymes that link bacterial capsule polymers to the outermembrane glycolipids, termed transition transferases, are identified, enabling reconstruction of the entire capsule biosynthesis pathway.

    • Christa Litschko
    • Valerio Di Domenico
    • Timm Fiebig
    ArticleOpen Access