Research articles

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.

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.

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.

Cui et al. developed LAUNCHER, a single-component switch using potyviral protease, which offers a high signal-to-noise ratio for precise payload release, enabling versatile cellular applications and enhanced synthetic circuit performance.

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.

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.

Ye et al. reveal the critical role of micropolarity in controlling the structure and miscibility of subcompartments in multiphasic biomolecular condensates, thereby providing new insights into multiphasic condensation regulation.

Development of chemically responsive bandpass filters mimics the signal-processing abilities of electronic circuits in mammalian cells by responding to chemical concentrations within a specific range and rejecting ones outside that range.

Methyl jasmonate in the root volatile organic compounds (rVOCs) signals to the soil microbiome to form biofilms with altered composition that benefits plant growth. This cross-kingdom VOCs-mediated signaling expands the zone of rhizosphere influence.

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.

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.

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.

The cryo-electron microscopy structure of the GPR101–Gs complex reveals the mechanism for its constitutive activity and facilitates the screening and identification of GPR101 ligands with rejuvenating potential.

Structural analysis of a type III effector protein CteC reveals that it represents a unique ‘D-E’ family of PARP-like ADP-ribosyltransferases, which harbors chimeric features from the enzymes of the R-S-E and H-Y-E classes.

Structural analysis of Crenotalea thermophila SPARTA reveals that guide-mediated target binding releases the auto-inhibition of SPARTA imposed by an acidic tail and triggers substantial conformational changes, resulting in the oligomerization of short Ago and TIR for SPARTA activation.

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.

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.

Development of live-cell target engagement approaches to query MEK-bound binary and ternary complexes reveals the distinct pharmacology of clinical MEK inhibitors at specific assemblies composed of MEK, RAF, KSR and 14-3-3.

Lis1 binding to the AAA+ ring of dynein increases the microtubule affinity and slows dynein motility. Lis1 binding to the stalk of dynein restricts the sliding of the coiled coils and slows detachment from microtubules under load.

A high-throughput DNA-encoded library (DEL)-based screening approach was developed for the discovery of proximity-inducing small molecules.