Articles in 2023

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.

Chemical proteomics profiling of 1,183 kinase inhibitors from past drug discovery projects revealed a large number of reasonably selective compounds for several kinases such as SYK and CK2.

The development of a transgenic mouse line that expresses mitochondrial matrix-targeted APEX2 combined with proteome analysis identified RTN4IP1, which serves as an NAD(P)H oxidoreductase required for respiration and CoQ biosynthesis.

NOXs are vital ROS-producing enzymes with roles in cell function and cancer. Here the authors combine computational and experimental methods to validate inhibitors for human NOX enzymes, opening avenues for redox biology-related cancer drug development.

A soluble bacterial transhydrogenase from Escherichia coli (EcSTH) was validated as a genetically encoded tool to induce NADH reductive stress in mammalian cells revealing unique transcriptional and metabolic signatures.

Park et al. redesigned the abscisic acid-induced dimerization module to respond to diverse ligands and function orthogonally to the natural modules, enabling synthetic biological circuit design in plants and yeast.

A controllable protease-based protein secretion platform was developed for the rapid delivery of user-defined therapeutic protein secretion in response to FDA-approved drugs, tumor antigen and light, enabling cell-based precision therapies.

A lipid-like small molecule, MAO-N₃, was developed to assemble inner mitochondrial membrane-specific probes for confocal and various super-resolution microscopy techniques, with significantly improved time-lapse capability and minimal toxicity.

Almost all terpenoids discovered so far have backbones made up of multiples of five carbon atoms. Here, the authors combine gene mining with biochemical characterization and chemical structure analysis to unveil an extensive class of terpenoids with 16 carbon atoms in bacteria.

A cell-based phenotypic screen led to the discovery of compounds called NVS-STGs, which bind to the N-terminal domain of STING and act as a molecular glue to induce higher-order oligomerization and activation.

Determining which covalent binding events impact protein function is challenging. Now, a strategy has been reported that integrates base editing and chemical proteomics to infer the functionality of ligandable cysteines in cancer dependency proteins by quantifying the impact of their missense mutation on cancer cell proliferation.

The flavoenzyme nicotine oxidoreductase degrades nicotine in the bloodstream. Now, genetic selection in bacteria has been used to improve the catalytic performance of nicotine oxidoreductase, isolating variants with increased O₂ reactivity that were more effective at degrading nicotine in the blood of rats.

Nou et al. engineered Bacillus subtilis cells into a living sentinel system, which can take up environmental DNA and fluoresce when a matching sequence is detected. This system enables recording of SNPs for facial features and has broad applications spanning forensics to agriculture.

Condensates have been proposed to create a distinct chemical solvating environment. In vitro condensate screens suggest that condensate chemical environments influence the intracellular distribution of small molecules.

This study reveals β-arrestin-independent GPCR signaling via the cAMP pathway from endosomes, and it delineates a discrete function of β-arrestin in temporally resolving the endosomal signaling phase as a separate peak of cytoplasmic cAMP.

Through directed evolution, the PAM compatibility of the compact Cas9 variant CjCas9 was increased. Evolved CjCas9 shows higher nuclease activity at canonical and non-canonical sites and enables robust in vivo gene editing from single AAV vectors.

Nitric oxide (NO) is a potent vascular signaling agent, but its bioavailability is limited through rapid scavenging reactions. DeMartino et al. characterize the formation and bioactivity of NO-ferroheme, a stable NO analog that forms readily, bypasses scavenging reactions and mediates NO signaling.