• 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.

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  • Macrocyclic peptides are promising scaffolds for chemical tools and potential therapeutics, but their synthesis is currently difficult. Here, the authors report the characterization of Ulm16, a peptide cyclase of the penicillin-binding protein (PBP)-type class of thioesterases, that catalyzes head-to-tail macrolactamization of nonribosmal peptides of 4–6 amino acids in length.

    • Zachary L. Budimir
    • Rishi S. Patel
    • Elizabeth I. Parkinson
  • A workflow integrating tools from bioinformatics, structural biology and synthetic biology has been developed that enables the rapid design of pili-enabled living materials. This approach allows mining of pili-producing nonpathogenic chassis, understanding of the pili structure and assembly, and engineering of pili-enabled living materials in a systematic and sequential manner.

    • Yuanyuan Huang
    • Yanfei Wu
    • Chao Zhong
  • Efforts to rationally engineer nonribosomal peptide synthetase (NRPS) enzymes have focused on making individual modifications. Here the authors describe a targeted random engineering approach that uses thousands of NRPS domains amplified from the soil metagenome for mass substitution experiments.

    • Sarah R. Messenger
    • Edward M. R. McGuinniety
    • Mark J. Calcott
  • Oxygen sensitivity hampers applications of metal-dependent CO2 reductases. Here, Oliveira et al. describe how an allosteric disulfide bond controls the activity of a CO2 reductase, preventing its physiological reduction during transient O2 exposure and allowing aerobic handling of the enzyme.

    • Ana Rita Oliveira
    • Cristiano Mota
    • Inês A. Cardoso Pereira
    • Small molecules and drugs are not homogenously distributed across cells, and are instead enriched in distinct subcellular compartments and membraneless biomolecular condensates. A new study lays out the path to identifying chemical features or ‘rationales’ that confer condensate-selective partitioning of small molecules.

      • Aseem Z. Ansari
      News & Views
    • Cells contain compartments composed of phase-separated protein condensates. We find that these condensates have a unique chemical microenvironment that enriches amphipathic metabolites such as phospholipids. Therefore, condensates are mixtures of proteins, nucleic acids and specific metabolites. The presence of phospholipids and other amphipathic metabolites might enable condensates to facilitate specific metabolic reactions.

      Research Briefing
    • Controlled interactions between macromolecules are fundamental regulatory layers. Hijacking these circuits via proximity-inducing small molecules offers many therapeutic opportunities. The organizers, Georg Winter and Cristina Mayor-Ruiz, report on the latest trends in this emerging field discussed at the 39th IRB-BioMed Conference in Barcelona.

      • Georg E. Winter
      • Cristina Mayor-Ruiz
      Meeting Report
    • Terpenoids bearing carbon skeletons derived from nonisoprene units are rare and considered noncanonical. Now, a genome-mining study has uncovered previously unknown noncanonical C16 terpenes and their biosynthetic pathways from bacteria. The findings suggest that noncanonical terpenoids are diverse and widespread in nature.

      • Shaonan Liu
      • Darwin Lara
      • Yang Hai
      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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