This Perspective details how genome-wide association studies and metabolomics enabled the discovery of structures, bioactivities and pathways of modular metabolite biosynthesis originates from the ‘hijacking’ of conserved detoxification mechanisms by nematodes.

Biased signaling gives hormones, probes or drugs distinct functional outcomes via the same receptor. The Biased Signaling Atlas (https://BiasedSignalingAtlas.org) provides a community hub with data and tools to advance this paradigm, which may yield safer and more potent drugs.

A new review article details how new structural insight regarding modular polyketide synthases (PKSs) helps us better understand the organization of catalytic events within a PKS module. The plausible models discussed will likely influence future PKS engineering efforts.

Tricyclic peptides have reduced conformational flexibility, making them well suited for ligand development. Researchers have now generated large combinatorial libraries of tricyclic peptides using a disulfide-directing motif. Screening these libraries discovered binders to challenging protein targets.

A carbon nanotube-based sensor was developed to monitor endolysosomal acidification events in live cells and in vivo. The technology enables a spatiotemporal measurement of endolysosomal pH and real-time tracking of the dynamics of autophagy in tumors.

A chemoproteomic approach is developed that examines changes in ligand binding-induced accessibility by globally labeling reactive proteinaceous lysines, revealing the cellular targets of glycolytic intermediates.

Wang et al. developed a bisulfite-free method termed DM-Seq that leverages an unnatural enzyme–substrate pair coupled with a DNA deaminase to sequence 5-methylcytosine at base resolution in sparse DNA samples, circumventing the limitations of chemical deamination methods.

Biochemical and structural analyses reveal how tetracenomycin X inhibits bacterial translation in a context-dependent manner that relies primarily on the presence of Gln-Lys motifs in the nascent polypeptide chain.

Phosphoribosyl pyrophosphate synthetase (PRPS1), an enzyme that regulates de novo nucleotide synthesis, was found to be O-GlcNAcylated, which increases PRPS1 activity, and is associated with increased tumorigenesis and resistance to chemoradiotherapy.

Fluorescent proteins and HaloTag allow the flexible design of FRET-based biosensors with adjustable color using different fluorescent proteins or fluorophores and readout can be modified to fluorescence intensity, lifetime or bioluminescence.