Reviews & Analysis

Comamonas testosteroni utilizes aromatic compounds such as monomers from lignin and plastics, but the underlying metabolic pathways were elusive. Multi-omics analysis now clarifies the multifaceted regulation of its metabolism, facilitating strain engineering to convert substrates from lignin and plastics into valuable bioproducts.

A modular platform was developed to generate designer condensates with tunable material properties for selective partitioning. These programmable assemblies can regulate bacterial plasmid expression and inheritance but will find a broad array of applications, including in eukaryote systems.

Ferroptosis can be induced by lipid peroxidation in various subcellular membranes, including the endoplasmic reticulum (ER), mitochondria and lysosomes. By studying the subcellular distribution of ferroptosis-modulating fatty acids, we observed that the ER is a key initial site of peroxidation, followed by the plasma membrane, whereas other organelles are not as critical for ferroptosis.

Etoposide, a chemotherapeutic poison of type IIA eukaryotic topoisomerases (topo IIs), promotes topo II to compact DNA by trapping DNA loops, creates DNA double-strand breaks, causes topo II to resist relocation, and pauses the ability of topoisomerases to relax DNA supercoiling. Through these mechanisms, etoposide converts topo II into a roadblock to DNA processing.

GPCRs are selective for specific G-protein subtypes, thereby ensuring signaling fidelity. A new report finds that that empty-like G-protein mutants are promiscuously recognized by GPCRs, suggesting that receptors select cognate over non-cognate G proteins at steps preceding nucleotide release.

Modern drug discovery relies upon intelligent exploration of ‘in stock’ and ‘on demand’ virtual libraries of compounds. A comparative analysis highlights the explosive expansion of accessible chemical space and also reveals challenges and opportunities arising for computational drug discovery.

Analysis of cell–cell communication between embryonic stem cells using a combination of experiments and modeling shows that cells can communicate important messages over much larger distances than previously known, exhibiting quorum-sensing-like behavior.

Small-molecule-mediated targeted protein degradation (TPD) relies on the recruitment of a target protein of interest to an E3 ligase. A new study indicates how direct target recruitment to the 26S proteasome can bypass this requirement.

Most engineered bacteria are designed to grow and function in a free-swimming state. A new method enables engineered bacteria to reversibly transition into a biofilm state.

A protein–protein interface between a peptide-recognition domain (Fyn-SH3) and catechol O-methyltransferase (COMT) is computationally designed to generate a highly selective peptide-modifying system. Detailed mechanistic analysis sets a gold standard for studying the complex kinetic properties of designer fusion proteins.

Inspired by nature, a synthetic carbon fixation cycle builds complex molecules directly from CO₂. Building metabolism from the ground up requires several innovative advancements — now, a strategy to balance carbon demands in a complex metabolic network is explored.

Bacteria utilize stringent factors to metabolize the nucleotide alarmone guanosine tetra-/pentaphosphate, or (p)ppGpp, for stress adaptation. Now, a distinct conformation of these factors explaining their regulation and specialization has been unveiled.

Major hurdles remain in understanding the mechanisms of multidrug resistance (MDR) protein efflux. A new study uses deep mutational scanning of a bacterial MDR protein to determine the nature of its drug-binding cavity and understand its function and plasticity.

High-mannose N-glycans are common post-translational modifications that occur on many proteins. The mechanism by which these high-mannose N-glycans are consumed by species of Bifidobacterium has now been characterized, which is important given their positive role in human gut microbiota and their abundance in breastfed infants.

This perspective proposes general strategies for phase-separation-related biological studies, including proper experimental designs to validate and characterize phase-separation phenomena, connections to biological functions and some caveats to avoid common misunderstandings.

Protein condensates are subcellular structures that enrich and confine molecules in cells. This Review details how condensates can be engineered with responsiveness and on-demand functions, thus pushing cellular and metabolic engineering to a new level.

This Review introduces molecular features of the phase-separating biomolecules and how they affect phase-separation behavior in a complex intracellular environment, highlighting a complex interplay between structure, sequence and environment in the phase-separation process.

Clustering and multimerization of cell surface proteins (CSPs) are essential for triggering downstream intracellular signaling events. Membrane-anchored liquid–liquid phase-separation systems have now been developed to manipulate the spatiotemporal distribution and activation of CSPs.

YcaO enzymes are able to catalyze a diverse set of reactions and have found industrial applications. New biochemical data provide the first direct evidence for the unified reaction mechanism proposed a decade ago and will inform future enzyme engineering efforts.

Ferredoxins are universal electron donors. A study focusing on the two human mitochondrial ferredoxins reveals the existence of unique cellular functions and partners for each protein.