• Drops of dew condensing on leaves

    This themed issue presents a collection of Reviews, Perspectives and Articles that aim to reveal the molecular and chemical principles underlying phase-separated condensate formation and promote the development and use of new tools for the study of phase separation biology.

Nature Chemical Biology is a Transformative Journal; authors can publish using the traditional publishing route OR via immediate gold Open Access.

Our Open Access option complies with funder and institutional requirements.


  • The kinesin-1 motor protein accesses open active and closed autoinhibited states. These states are regulated by a flexible elbow within a complex coiled-coil architecture. Now, a conformational switch has been developed by engineering the elbow to create a closed state that can be controllably opened with a de novo designed peptide to increase kinesin transport inside cells.

    • Jessica A. Cross
    • William M. Dawson
    • Derek N. Woolfson
    ArticleOpen Access
  • Toxic small alarmone synthetase (toxSAS) enzymes are toxic effectors of certain toxin–antitoxin modules, involved in phage defense and secretion systems. Here the authors establish the mechanism underlying toxSAS inhibition by structured antitoxins and reveal the connection between neutralization strategy and substrate specificity.

    • Lucia Dominguez-Molina
    • Tatsuaki Kurata
    • Abel Garcia-Pino
    ArticleOpen Access
  • Enediyne natural products are potent antitumor antibiotics but the biosynthesis of their 1,5-diyne-3-ene core has remained enigmatic for decades. Here a diiodotetrayne is reported as a universal enediyne biosynthetic intermediate of this core, obtained upon cryptic iodination.

    • Chun Gui
    • Edward Kalkreuter
    • Ben Shen
  • A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

    • Nathan M. Ennist
    • Shunzhi Wang
    • David Baker
    ArticleOpen Access
  • Jiang et al. developed a computational method to design repeat proteins with multiple structured loops that are buttressed by extensive hydrogen bond networks. The designs were further functionalized into high-affinity peptide-binding proteins.

    • Hanlun Jiang
    • Kevin M. Jude
    • David Baker
    ArticleOpen Access
    • Fluorogenic RNA aptamers have previously been developed to enhance RNA imaging. We determined the tertiary complex structures of a newly discovered Clivia aptamer, which exhibits a small size and a large Stokes shift. Structural insights into the fluorescence activation mechanism of Clivia build a strong foundation for its efficient use in RNA imaging.

      Research Briefing
    • To understand the complex dynamics and diverse functions of RNA, robust technologies for labeling and imaging RNA are highly desirable. A newly developed green fluorescent aptamer named Okra enables the imaging of mRNA dynamics in living cells.

      • Dhrisya Sathyan
      • Murat Sunbul
      News & Views
    • We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody–peptide inhibitor conjugates (APICs) that target a family of proteases, the cysteine cathepsins. Our drug design and targeted delivery approach ensure specific inhibition and achieve therapeutic efficacy in different cancer cells and osteoclasts.

      Research Briefing
    • The ZDHHC family of palmitoyl transferases lipidates numerous protein targets, but the paucity of selective inhibitors has hindered their target profiling. A generalized chemical genetic system can now map the protein targets of individual ZDHHC family members.

      • Tong Lan
      • Bryan C. Dickinson
      News & Views
    • Targeted protein degradation has emerged as a promising approach in drug discovery, harnessing a cell’s intrinsic machinery to eliminate disease-related proteins. Now, a study paves the way to translating this technology into potential anti-mycobacterial therapies, by exploiting the bacterial protein-degradation complex.

      • Delia Preti
      • Valentina Albanese
      • Peggy Carla Raffaella Marconi
      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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