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  • Artistic representation of a protein gel with the bands showcased in bright colours.

    Our June 2025 issue featured a collection of articles that explored emerging research in the continual interplay between chemical biology and metabolism.

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  • An ‘intracrine’ signaling mechanism is proposed whereby a G-protein-coupled receptor (free fatty acid receptor 4) senses locally released fatty acids on intracellular membranes associated with lipid droplets to efficiently regulate lipolysis in adipocytes.

    • Shannon L. O’Brien
    • Emma Tripp
    • Davide Calebiro
    ArticleOpen Access
  • LaccID, an engineered laccase, enables hydrogen-peroxide-free proximity labeling and electron microscopy (EM) in mammalian cells. Notably, LaccID is selectively active at the cell surface, enabling the mapping of the dynamic T cell–tumor surfaceome and its use as a genetically encodable EM tag, expanding the toolkit for cell-based imaging and proteomics.

    • Song-Yi Lee
    • Heegwang Roh
    • Alice Y. Ting
    ArticleOpen Access
  • Structural studies of certain Tn and STn antigen-targeting antibodies reveal that their VH and VL domains recognize the glycan antigen and the adjacent peptide region, respectively, enabling a VH domain-focused and VL domain-varying phage display library to generate antibodies targeting diverse glycopeptide epitopes.

    • Ramon Hurtado-Guerrero
    • Spyridon Gatos
    • Ola Blixt
    Article
  • The primary entry route of vanilloid ligands to the vanilloid-binding site in transient receptor potential vanilloid 1 (TRPV1) is found to be a distinct and targetable hydrophobic pathway at the TRPV1–cell membrane interface rather than through direct membrane penetration.

    • Meng-Yang Sun
    • Yu-Jing Bian
    • Ye Yu
    Article
    • The discovery of lipoamide offers a unique approach to modulate stress granule dynamics. It will advance studies of stress granule biology and inform the therapeutic modification of these biomolecular condensates as a potential treatment option for amyotrophic lateral sclerosis.

      • Alicia Dubinski
      • Christine Vande Velde
      News & Views
    • Self-labeling protein tags (SLPs) have revolutionized bioimaging by enabling precise protein tracking. A next-generation SLP, SNAP-tag2, has now been developed with improved labeling kinetics, fluorescence brightness, and substrate accessibility. These enhancements enable deeper insights into cellular processes in the field of bioimaging.

      • Masayasu Taki
      • Masayoshi Nakamura
      News & Views
    • Promyelocytic leukemia (PML) nuclear bodies (NB) facilitate the proteasomal degradation of protein aggregates through the SUMO-targeted ubiquitin ligase pathway. A study now reveals a non-proteolytic role for PML-NBs in preventing TDP-43 aggregation that still relies on the SUMOylation–ubiquitylation cascade but uses it to direct protein aggregates towards p97 ATPase-mediated disaggregation.

      • Xiaoyang Yu
      • Huaiying Zhang
      News & Views
    • The development of antibody–drug conjugates remains a challenge in part due to the lack of three-dimensional structural information that must account for the inherent flexibility of antibodies and drug payloads. This Perspective discusses computational methods to guide the design of antibody–drug conjugates.

      • Anastasia Croitoru
      • Asuka A. Orr
      • Alexander D. MacKerell Jr.
      Perspective
    • The discovery of seven soybean genes completes the biosynthetic pathway to major glyceollins, granting access to heterologous production and exploration of their antimicrobial potential.

      • Lee Marie Raytek
      • Mehran Dastmalchi
      News & Views

Chemical Biology of Microbiomes

Interspecies communication in complex microbiome environments occurs through the small molecules, peptides, and proteins produced by both the host and the microbial residents, as highlighted in this collection of recent articles from Nature Portfolio.
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