Volume 19 Issue 5, May 2023

Anaerobes have developed unique metabolic pathways and strategies, some of which are still not well understood. Now, a study that integrates spectroscopy with dynamic metabolic modeling reveals the metabolism of the anaerobic pathogen Clostridioides difficile.

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.

Substrate–inhibitor conjugation facilitates structural determination of the KDM2A/B-nucleosome complexes, which provides mechanistic insights into the nucleosomal H3K36 demethylation by KDM2A/B and reveals a paralog-specific nucleosome acidic patch recognition mechanism mediated by the N terminus of KDM2A but not KDM2B.

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.

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.

A machine-learning method called MetalNet was developed to systematically predict metal-binding sites in proteomes using sequence co-evolution, which enabled the identification of new metalloproteins.

Live-cell HRMAS NMR spectroscopy and genome-scale metabolic modeling enable high-resolution analysis of dynamic, anaerobic metabolism in Clostridioides difficile, identifying the confluence of carbohydrate and amino acid fermentations for alanine synthesis.

Heparan sulfate proteoglycans are extended disaccharide co-polymers containing decorations of sulfation and epimerization linked to cell surface and extracellular matrix proteins that contribute to cell signaling and tissue homeostasis. This structural and mutagenic study on the EXT1–2 complex explains molecular details of the backbone co-polymer synthesis.

Tryptophan C-mannosyltransferase (CMT) enzymes append a mannose to the first tryptophan of select sequences, which is important for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. A study reveals the structure, mode of peptide recognition and catalytic mechanism for the eukaryotic C-mannosyltransferase DPY19.

DNA damage results in the acetylation of the cell-cycle checkpoint kinase WEE1 at Lys177 enabling activation. The deacetylase SIRT1 directly associates with and modifies WEE1 to inactivate it enabling resistance to WEE1 inhibition in cancer cells.

Development of a quantitative approach to determine how far a signal from a cell travels as a diffusible molecule reveals a millimeter-scale quorum sensing mechanism that determines collective growth of differentiating embryonic stem cells.

A near-atomic resolution strain-specific cryo-EM structure of infectious prion fibrils from mice was determined, revealing a structural definition for intra-species prion strain-specific conformations.

A bifunctional amino acid, photo-ANA, equipped with a bio-orthogonal handle and a photoreactive warhead, specifically labels Salmonella spp. during infection and enables the profiling of proteome dynamics and host–pathogen protein–protein interactions.

Spangler et al. used a substrate inhibitor covalent conjugate strategy to solve cryo-EM structures of nucleosomes in complex with the lysine demethylase KDM2, which demonstrates that KDM2A, but not its closely related paralog, KDM2B, anchors to the acidic patch to direct histone H3K36-specific demethylation.

A new biosynthetic core-forming enzyme, arginine cyclodipeptide synthase (RCDPS), was found to produce cyclo-arginine-Xaa dipeptides via a tRNA-dependent mechanism, and further genome mining using RCDPS as a beacon uncovered new natural products.

Using single-molecule biophysics methods, Le et al. discovered that etoposide, a chemotherapeutic poison of topoisomerase II (topo II), promotes topo II to compact DNA, trap DNA loops and pause DNA supercoiling relaxation, thus converting topo II into a strong roadblock to DNA processing.

Aromatic carbon fluxes for the metabolism of lignin and plastics derivatives in Comamonas testosteroni KF-1 are controlled by pathway-specific regulation at transcript, protein or metabolite levels. The combination of transcriptional activation and metabolic fine-tuning complicates predictions of modulated carbon and energy fluxes during metabolic engineering strategies.