Volume 19 Issue 2, February 2023

Unbiased metabolomics revealed the conversion of serotonin into N-acetylserotonin-derived glucosides by an intestinal carboxylesterase in Caenorhabditis elegans, which suggests an unappreciated role of the gut in modulating 5-HT signaling.

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.

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.

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.

The combination of cryo-electron microscopy analysis with cell-signaling assays revealed promiscuous G_i/G_q coupling of somatostatin receptors and molecular mechanism of ligand-dependent selective G protein signaling

Untargeted comparative metabolomics revealed serotonin biosynthesis and metabolism pathways in nonneuronal tissues that contribute to established serotonin-dependent phenotypes in C. elegans.

Structure and mutagenesis of the colibactin-activating peptidase ClbP reveals a dimer with a substrate-binding transmembrane domain and a conserved polar network in its periplasmic domain that enforces selectivity for d-asparagine prodrug motifs.

A substrate-guided design strategy generated highly potent inhibitors of the biosynthesis of the genotoxin colibactin by human gut bacteria. These inhibitors also enable a generalizable approach for chemically guided natural product discovery.

Anaplerotic reactions constantly refill metabolic networks with essential intermediates. This concept was adapted to enable a 54-step in vitro biosynthesis of the macrolide backbone of the antibiotic erythromycin from CO₂.

Base editor technology combined with a fluorescent reporter of DNA methyltransferase activity enable in situ mutational scanning of DNMT3A, revealing a requirement of DNA binding by the PWWP histone reader domain for full activity.

Tan et al. reveal that a class of lipids, 3-sulfogalactosyl diacylglycerols, decrease in the central nervous system with aging. 3-sulfogalactosyl diacylglycerols are present in the human brain and suppress inflammation suggesting these lipids may play a role in age-related diseases and inflammation.

By designing a fluorescent protein with a well characterized non-native ensemble, which captures the structural modulation of a substrate by the Hsp70/DnaJ/NEF system, Tiwari et al. resolved the individual steps of the disaggregation unfolding mechanism of Hsp70.

Mitochondrial ferredoxins FDX1 and FDX2 are assigned to specifically donate electrons to steroidogenesis, Fe–S protein biogenesis, heme a formation or lipoylation. The proteins’ functions can be swapped by mutually exchanging short peptide segments.

The human gut Bifidobacterium longum can use host N-glycans as carbon and energy sources via a specific and cooperative multienzymatic system.

Murray et al. identified and characterized a small-molecule inhibitor of human COQ8A, which belongs to the UbiB protein family and is essential for coenzyme Q biosynthesis.

A small molecule was developed that disrupted the lipid–SH2 domain interaction of the spleen tyrosine kinase (Syk), suppressed oncogenic activities in acute myeloid leukemia cell lines and was refractory to drug resistance.