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Structural characterization of the amino-acid-modifying radical halogenase BesD and identification of new members of this protein family provides insight into the enzymatic mechanism and enables biocatalytic production of halogenated amino acids.
A 2H and 13C tracing strategy was used for efficient determination of glycolytic thermodynamics, revealing near-equilibrium glycolytic steps enabling rapid flux adaptation and, in Clostridium cellulolyticum, enhanced ATP yield.
KAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase activity.
Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty acids.
Single-molecule analysis revealed that the velocity and force generation of the mammalian dynein–dynactin complex is regulated by activating adaptors and tail–tail interactions between two dyneins.
An in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in vivo.
A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC recycling.
Via its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon growth.
The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent dioxygenase.
A light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian cells.
Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.
Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of sepsis.
The iron chaperone poly(rC)-binding protein 1 (PCBP1) coordinates ferrous iron via its KH3 domain and, together with BolA2 and glutathione, forms a complex that is required for the assembly of [2Fe–2S] clusters on the cytosolic BolA2–Glrx3 chaperone.
Split Cpf1 pairs are identified to enable chemical- and light-induced genome editing via dimerization. Another pair of split Cpf1 can be used to activate gene expression with high efficiency in cells and in mice.
Small molecule or light-inducible gene circuits in Escherichia coli enable asymmetric cell pole localization of diguanylate phosphodiesterase and facilitate asymmetric cell division regulated by c-di-GMP-responsive transcription factors.
The indolmycin biosynthetic pathway in a marine gram-negative bacterium is distinct from its counterpart in terrestrial gram-positive Streptomyces species, using a Streptomyces shunt product as a substrate for an N-demethylindolmycin synthase.
The chromosomal partitioning system (par) of Caulobacter crescentus was repurposed to create an inducible genetic circuit for asymmetric plasmid partitioning and cell division in Escherichia coli.
Structural and biochemical characterization of the spirochaete flagellar hook protein FlgE reveals how cysteine and lysine residues spontaneously react to form an interdomain lysinoalanine crosslink without the involvement of additional enzymes.
Fusion of Cas9 with m6A writers METTL3 and METTL14 or eraser ALKBH5 enables site-specific writing or erasing of RNA m6A modifications in mammalian cells and investigation of individual m6A modification-mediated function.
A bacterial 2-hydroxyacyl-CoA lyase catalyzes ligation of carbonyl-containing molecules of different chain lengths with formyl-CoA to produce elongated 2-hydroxyacyl-CoAs, enabling a one-carbon bioconversion pathway with formaldehyde as a substrate.