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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.
Using a thiol-reactive probe, chemoproteomic profiling of cysteine targets of itaconate reveals the covalent modification of glycolytic enzymes, impairing glycolytic flux and contributing to attenuation of the inflammatory response in macrophages.
Male C. elegans excrete an N-acylated glutamine that acts via evolutionarily conserved nuclear hormone receptor and chemosensory pathways to counteract dauer diapause and accelerate sexual maturation of hermaphrodites, at the cost of shortening hermaphrodite lifespan.
The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to CHIP.
Use of DNA-origami nanostructures to study lipid transfer between closely apposed membrane bilayers supports a model where phospholipids are transferred by extended synaptotagmin 1 between the endoplasmic reticulum and plasma membrane through a shuttle mechanism.
Characterization of multiple enzymes involves in biosynthesis of the aminocyclitol antibiotic pactamycin reveals a key step involving the glycosylation of an acyl carrier protein-bound intermediate by the promiscuous glycosyltransferase PtmJ.
The TransATor application bioinformatically predicts chemical structures for the products of trans-acyltransferase polyketide synthases, enabling the characterization of new polyketide natural products from (unusual) bacterial sources.
Elucidation of a multi-enzyme pathway for degradation of the polysaccharide ulvan by Formosa agariphila provides tools to use ulvan biomass from marine algal blooms as feedstock for renewable sources of carbohydrates.
A chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia cells.
A covalent ligand that targets C277 of ATP6V1A was identified resulting in enhanced v-ATPase activity, inhibition of mTORC1 signaling, increased lysosomal acidification, activation of autophagy and clearance of toxic protein aggregates.