Research articles

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  • 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
  • Here, the authors describe the mechanistic flexibility and substrate promiscuity of the apramycin resistance enzyme ApmA. They identify additional clinical drugs susceptible to modification through a molecular mechanism that diverges from other enzymes within the left-handed β-helix superfamily.

    • Emily Bordeleau
    • Peter J. Stogios
    • Gerard D. Wright
  • Dumelie et al. asked whether biomolecular phase-separated condensates can establish microenvironments with distinct metabolomes and found that amphipathic lipids are highly enriched in these microenvironments and influence the properties of the condensates.

    • Jason G. Dumelie
    • Qiuying Chen
    • Samie R. Jaffrey
  • A chemical screen identified a small molecule inhibitor of CHEK2 that boosts insulin secretion in human β cells, including those from both healthy and type 2 diabetic human islets, as well as in diabetic mouse models and cynomolgus macaques.

    • Angie Chi Nok Chong
    • J. Jeya Vandana
    • Shuibing Chen
    ArticleOpen Access
  • Cofactorless oxygenases are rare in nature and natural product biosynthesis. Here the authors describe the biochemical and structural characterization of two such oxygenases catalyzing deformylation, ring cleavage and epoxidation in the biosynthesis of the enediyne natural product tiancimycin A.

    • Chun Gui
    • Edward Kalkreuter
    • Ben Shen
  • Hydrogen–deuterium exchange–mass spectrometry and cryo-EM analysis revealed an allosteric mechanism involving the conformation of a single α-helix that controls the global conformation and activity of eIF2B, the core molecular machine of the integrated stress response.

    • Rosalie E. Lawrence
    • Sophie R. Shoemaker
    • Peter Walter
    ArticleOpen Access
  • Zhang et al. determine multiple cryo-electron microscopy structures of inactive monomeric and active tetrameric short prokaryotic Ago/TIR–APAZ (SPARTA) complexes, providing structural basis of SPARTA assembly and activation that will facilitate the development of SPARTA-based biotechnological tools.

    • Jun-Tao Zhang
    • Xin-Yang Wei
    • Ning Jia
  • A yeast platform for de novo biosynthesis of medicinal plant compounds has now been reported. The platform was used to explore the biocatalytic potential of refactored plant pathways and resulted in the production of 19 halogenated derivatives with therapeutic potential.

    • Samuel A. Bradley
    • Beata J. Lehka
    • Michael K. Jensen
    ArticleOpen Access