Reviews & Analysis

Using new letters of DNA to encode information promises to expand the genetic code in a transformative way. A new semisynthetic organism has been created that uses 67 codons for protein biosynthesis, with three new codons based on unnatural nucleotides.

Ferroptosis induced by GPX4 inhibition offers promise for killing drug-resistant cancer cells, yet current GPX4 inhibitors lack selectivity. The discovery of masked nitrile oxide electrophiles as selective prodrug inhibitors of GPX4 points to an attractive path for chemically inducing ferroptosis.

This Perspective describes the chemical and biophysical principles common to all bifunctional, proximity-inducing small molecules. It also discusses the underappreciated diversity of their chemical structures and biological mechanisms.

Phospholipase D (PLD) regulates various cellular functions through the signaling lipid phosphatidic acid (PA). New crystal structures of human PLD1 and PLD2 reveal a catalytic mechanism, inhibitor binding, and regulation, enabling future structure-based inhibitor design and functional studies of PLD.

Tyrosine sulfation is a common post-translational modification known to play critical roles in multiple bioprocesses. A cleverly engineered mammalian expanded genetic code now enables the direct co-translational incorporation of tyrosine sulfates into proteins to study their function in cellular contexts.

The mechanisms by which bioactive drugs get into their target cells is a question that has been greatly neglected. A new survey with CRISPR–Cas9 shows the widespread importance of protein transporters called solute carriers (SLCs).

Characterization of biased receptor signaling has ushered in opportunities for unprecedented control of G-protein-coupled receptors. Elucidation of distinct M1 muscarinic acetylcholine receptor signaling pathways and development of biased ligands may offer novel and safer Alzheimer’s disease therapeutics.

Cryo-EM and Cryo-ET have emerged as useful tools to study the efficient and dynamic processes of the viral assembly.

Retro-2 is a drug that protects cells against bacterial and plant toxins by arresting their trafficking in endosomes. New data show that the target for Retro-2 is surprisingly not within the endosomal system, but on the endoplasmic reticulum.

The traditional function of pseudouridine synthases is to convert uridine residues in RNA to pseudouridines. A study reveals a new function for the human PUS10 protein, which enhances micro-RNA maturation in addition to tRNA modification.

Engineered living materials (ELMs) with the qualities of both programmable functionalities and environmental tolerance are rare. 3D printing of bacterial spores into resilient living materials provides a viable route to fabricate ELMs that integrate these material attributes.

The native stress-tolerant phenotypes of various non-conventional microbes have the potential to enable more efficient bioprocessing for chemical production, addressing certain design challenges encountered when using model production hosts.

The site-specific monoubiquitination of FANCD2 is crucial for the Fanconi anemia DNA repair pathway and tumor suppression. This modification is mediated by the E2 enzyme UBE2T and the E3 ligase FANCL through a novel allosteric mechanism.

Genetic screens uncover a bioactivation pathway for Lasonolide A involving enrichment in lipid droplets and cleavage into a cytotoxic, soluble metabolite by a lipid droplet-associated serine hydrolase. These findings identify enzymatically regulated phase partitioning as a drug activation mechanism.