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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.

Polymerase Bcs3, which allows the fermentation-free synthesis of Haemophilus influenzae type b capsule for vaccine development, adopts a basket-like shape with all six active sites facing the interior, creating a protected environment for catalysis.

We used chemical proteomics to identify candidate protein targets of indole metabolites in mammalian cells. We discovered that microbiota-derived and synthetic aromatic monoamines can activate recruitment of β-arrestin to the orphan receptor GPRC5A. Specific microbiota species that express amino acid decarboxylases were found to produce aromatic monoamine agonists for GPRC5A.

A new platform for screening nucleophilic-fragment-based covalent ligands enables the identification and targeting of ligandable sulfenic acid sites, setting the stage for exploration of nucleophile-directed probe and drug development.

Systematically culturing combinations of auxotrophic yeast mutants leads to the identification of pairs that form obligatory cross-feeding relationships, some of which are stable over time and can divide metabolic labor for biotechnological applications.

The use of chemical proteomics and cell-based assays enabled the discovery of gut microbiota-derived aromatic monoamines and synthetic agonists for an orphan G protein-coupled receptor GPRC5A that stimulated beta-arrestin recruitment.

Chemoproteomics reveals a vast expanse of ligandable cysteine sulfenic acids in the human proteome, highlighting the utility of nucleophilic small molecules in the fragment-based covalent ligand discovery pipeline.

Lowering the levels of disease-promoting proteins is generally assumed to be beneficial. The authors developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic locus. This approach was used to study the effect of BACH1 levels on MDA-MB-231 human breast metastatic cells.

Using a neural network trained on bacterial growth inhibition data, in silico prediction of molecules with activity against Acinetobacter baumannii led to the identification of the narrow-spectrum abaucin, which perturbs lipoprotein trafficking.

The structure, molecular and mechanistic details of the human α1,3-fucosyltransferase FUT9 provide insight into the synthesis of diverse and modified glycan-capping Lewis antigen structures by a conserved family of mammalian fucosyltransferases.

Protein stability is important for biological function, but little is known about in-cell stability. In the New Delhi metallo-β-lactamase NDM-1, enhancement of zinc binding or amino acid substitutions at the C terminus increase in-cell kinetic stability and prevent proteolysis. These findings link NDM-1-mediated resistance with its in-cell stability and physiology.

The medicinal plant Catharanthus roseus is a source of leading anticancer drugs. The monoterpene indole alkaloid (MIA) biosynthetic pathway in C. roseus has now been analyzed using a complementary, multi-omics, single-cell approach. This identified clusters of genes involved in MIA biosynthesis and cell-type-specific partitioning in the MIA biosynthetic pathway.

Identification of the molecular features that define the kinetic stability of the clinically relevant NDM-1 metallo-β-lactamase in the bacterial periplasm links the cellular metabolism of this protein with its natural evolution.

A combination of enzyme discovery for nonheme diiron N-monooxygenases, metabolic engineering and genetic code expansion enables the construction of a live bacterial producer of synthetic nitrated proteins containing para-nitro-l-phenylalanine.