queuine (STEL-101) / Stellate Therap - LARVOL DELTA

Exploring overlooked growth-promoting mechanisms by plant-associated bacteria. (PubMed, Sustain Microbiol) - "This process also releases macromolecules that are digested in the environment, releasing key metabolites such as queuine, an important base analog present in the anticodon of some transfer RNAs. This overlooked importance of cell lysis could also be a major cause of the ubiquitous presence of bacteriophages in microbiota."

Journal • Review

tRNA methyltransferase (TRDMT1/DNMT2) participates in network of RNA modification in the Moss Physcomitrium patens. (PubMed, Biochim Biophys Acta Proteins Proteom) - "On the basis of the results obtained we propose that pathways leading to m7G46 modification by tRNA-Guanine-N-7-methyltransferases and incorporation of Queuine by QTRT1 may be modulated at transcriptional/post-transcriptional levels by PpTRDMT1/PpDNMT2 function in P. patens. SIGNIFICANCE STATEMENT: tRNA modifying enzymes form a network in the moss P. patens."

Journal • TRDMT1 • WDR4

Gut microbiota dysbiosis in COPD patients increases the level of queuine in the blood serum abnormally enhancing the viability of lung epithelial cells. (PubMed, Front Immunol) - "Excess queuine enhances cell viability of smoke-exposed lung cancer epithelial cells and is associated with increased pulmonary nodules in vivo. These findings identify queuine as a microbiota-derived metabolic mediator that may connect COPD-related dysbiosis to abnormal proliferation of lung epithelial cells."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Queuine tRNA ribosyltransferase 1 deficiency ameliorates hepatic steatosis and atherosclerosis possibly via modulating lipogenesis. (PubMed, Genes Dis) - No abstract available

Journal • Atherosclerosis • Cardiovascular

Microbiome-derived queuine vitamers underlie tyrosine metabolism and predator avoidance in mosquito larvae. (PubMed, Commun Biol) - "Likely due to effects on movement and behavior, Q-deficient larvae exhibit impaired predator evasion, resulting in increased capture by predaceous beetle larvae. The broad effects of Q-deficiency in mosquito larvae highlight the importance of previously unexplored microbiome-derived nutrients for mosquito physiology and behavior."

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Defective queuosine and i6A/ms2i6A modification of tRNATyr cause frameshifting and protein aggregation. (PubMed, Nucleic Acids Res) - "In bacteria, Q34 is synthesized de novo, whereas eukaryotes obtain queuosine (Q) or its precursor queuine (q) from external sources...In S. pombe, Q34 enhances tRNATyr abundance in tit1∆ cells and reduces i6A37 levels in wild-type, revealing reciprocal regulation. Together, these findings demonstrate a synergistic role of Q34 and (ms2)i6A37 in maintaining translational fidelity and proteostasis, with potential implications for human health when Q availability is limited."

Journal • CNS Disorders • Psychiatry • Schizophrenia

The exercise-microbiota-queuine-tRNA axis in Parkinson's disease: evidence, uncertainties, and experimental priorities. (PubMed, Front Neurosci) - "Finally, we outline experimental priorities for validating this model, including direct Q-tRNA profiling in PD tissues and biofluids, exercise-intervention studies in PD models, microbiota/queuine manipulation, and mechanistic testing of circulating RNA carrier transport across the blood-brain barrier. This framework does not establish a new pathogenic pathway, but provides a structured roadmap for investigating how exercise, microbial metabolism, and RNA modification biology may converge on selective neuronal vulnerability in PD."

Journal • Review • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Queuine Replacement Uncovers a Novel Approach to Suppress T Cell and B Cell Responses in Rheumatoid Arthritis (EWRR 2026) - "In parallel, queuine replacement limits B cell proliferation and costimulatory capacity, including TNF-mediated and cell contact-dependent signals. These findings identify AVK1-110-mediated queuine replacement as a promising immunomodulatory approach for autoimmune diseases such as RA and support further evaluation in patient-derived models."

IO biomarker • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCR7 • CD40LG • CD69 • CD80 • HIF1A • ICAM1 • IFNG • IL17A • IL2 • IL2RA • KLRB1 • SLC2A1

Novel Suppression of RA-FLS Pathogenic Behaviours at the Translational Level using Queuine Analogues (EWRR 2026) - "Conclusion The use of the Queuine analogue AVK1-110 reduced the proinflammatory, invasive, and immune-cell recruiting phenotype of the RA-FLS, whilst inducing a stark shift towards a more metabolically quiescent phenotype. These findings highlight a potential novel avenue of therapeutic intervention at the translation level for suppression of FLS pathogenicity and immune-cell interactions in RA."

IO biomarker • Immunology • CD55 • CXCR4 • FAP • ICAM1 • IL6 • PD-L1 • THY1 • VCAM1

Enzyme-Mediated Covalent Labeling Enables In Situ Imaging of RNA Modification States. (PubMed, J Am Chem Soc) - "Using this approach, we track queuine incorporation and loss kinetics across cell lines, analyze genetic factors that control modification, and resolve differences between cytosolic and mitochondrial tRNA populations. Beyond queuine, this work demonstrates a strategy for converting the endogenous RNA modification state into a covalent fluorescent readout, providing a chemical framework for spatial analysis of RNA modifications in intact cells."

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Microbiota-derived indole differentially shapes Entamoeba histolytica physiology and promotes host-compatible colonization. (PubMed, PLoS Negl Trop Dis) - "We previously showed that bacterial metabolites such as queuine and oxaloacetate modulate parasite stress responses and virulence...Infection with WT + I trophozoites induced higher CXCL1 and lipocalin expression than ADI trophozoites, indicating a stronger host inflammatory response to acutely indole-exposed parasites. These findings identify indole as an ecological cue that initially challenges E. histolytica but, upon sustained exposure, promotes adaptive reprogramming toward enhanced stress tolerance and improved host-compatible colonization."

Journal • Infectious Disease • Inflammation • CXCL1

Effect of Social Rank on Gut Microbes and Their Metabolites of Greater Long-Tailed Hamsters (Tscherskia triton). (PubMed, Integr Zool) - "Social rank strongly shaped gut microbiota and metabolic output: dominants were enriched in energy-harvesting taxa (e.g., Limosilactobacillus and Alistipes) and had higher fecal queuine levels, a metabolite derived from gut microbiota...These findings suggest that dominance in solitary species may be supported by coordinated host-microbiome interactions, which meet high energetic demands while maintaining stress resilience. This provides a novel framework for understanding the gut-brain-microbiome axis in social dominance."

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Disrupted tRNA modification leads to intestinal mitochondrial dysfunction and microbial dysbiosis. (PubMed, bioRxiv) - "Our previous study demonstrated tRNA modopathies and altered queuine-related metabolites in inflammatory bowel diseases...Restoring mitochondrial function leads to enhanced QTRT1. Targeting tRNA-Q modification in enhancing mitochondrial function will be a novel method to maintain intestinal health."

IO biomarker • Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • BAX • BCL2 • CASP3 • CD14 • CDC42 • MUC2 • TJP1

Decoding tRNA dynamics in neuroimmune disorders: mechanistic insights, diagnostic innovations, and therapeutic opportunities. (PubMed, Front Immunol) - "We highlight innovative diagnostic biomarkers (e.g., plasma tsRNAs, aminoacyl-tRNA synthetase-interacting multifunctional protein 1) and therapeutic strategies targeting tRNA modification pathways (e.g., queuine analogs, tRNA ligase inhibitors). By bridging tRNA biology with neuroimmunology, this work underscores the translational potential of tRNA-centric approaches in managing complex neurological diseases."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Parkinson's Disease • Rare Diseases

Microbial metabolites shape mammalian protein translation. (PubMed, Cell Metab) - "In a recent issue of Nature Cell Biology, Zhang et al. show that pre-queuosine 1 (preQ1), an intermediate of the bacterial queuine biosynthesis pathway, competes with queuine for the same mammalian tRNA targets to antagonistically modulate protein translation and cell proliferation."

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In silico screening and in vitro biological evaluation reveal Queuine as a promising MAP4K4 inhibitor for treating pancreatic cancer. (PubMed, BMC Biotechnol) - No abstract available

Journal • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor

Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control. (PubMed, Nat Cell Biol) - "The microbiome affects eukaryotic host cells via many metabolites, including the well-studied queuine as substrate for host tRNA queuosine modification...We identify the endoplasmic reticulum-localized inositol-requiring enzyme 1 (IRE1) ribonuclease as the enzyme responsible for the selective degradation of preQ1-modified tRNAs on translating ribosomes. Our results identify two microbial metabolites competing for host tRNA modification, which elicits translation quality control and impacts cell proliferation."

Journal • Oncology • ERN1

Selective Chemical Manipulation of Mannosyl- and Galactosyl-Queuosine in tRNAs of Living Cells. (PubMed, Angew Chem Int Ed Engl) - "Here, we performed feeding experiments with synthetic deoxyqueuine derivatives that lack either the allylic, the homoallylic, or both hydroxyl groups. Analysis of the queuosine derivatives that are found in the corresponding tRNAs shows that the glycosylases attach the sugar with precise specificity, suggesting decisive functions of the galactose and mannose sugar moieties in the decoding process."

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The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine. (PubMed, Proc Natl Acad Sci U S A) - "Ectopic expression of labeled SLC35F2 reveals localization to the cell membrane and Golgi apparatus via immunofluorescence. Competition uptake studies show that SLC35F2 is not a general transporter for other canonical ribonucleobases or ribonucleosides but selectively imports q and Q. The identification of SLC35F2, an oncogene, as the transporter of both q and Q advances our understanding of how intracellular levels of queuine and queuosine are regulated and how their deficiency contributes to a variety of pathophysiological conditions, including neurological disorders and cancer."

Journal • CNS Disorders • Oncology • Psychiatry • Schizophrenia • SLC35F2

Mammalian queuosine tRNA modification impacts translation to enhance cell proliferation and MHC-II expression. (PubMed, J Mol Biol) - "Eukaryotic tRNA Q-modification requires the metabolite queuine - derived from diet or catabolism of the gut microbiome - and a host-genome encoded enzyme complex, QTRT1/QTRT2...We also find that tRNA Q-modification increases surface presentation of MHC-II in BMDCs. Our results provide insights into the broader implications of tRNA Q-modifications in regulating diverse biological functions."

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Metabolomic and Molecular Insights into ATP Synthase Inhibitors from Micromonospora sp. as Novel Antimicrobial Agents Against Multidrug-Resistant Gram-Negative Pathogens of Enteric Origin. (PubMed, Lett Appl Microbiol) - "Further analysis using LC-QTOF-MS/MS non-targeted metabolomics identified six bioactive compounds-melibiose, oligomycin A, queuine, heptelidic acid, diethyl phthalate, and 2'-deoxyguanosine-linked to the inhibition of bacterial enzymes essential for proliferation...This study integrates metabolomics, molecular docking, and genomics, offering robust mechanistic insights into ATP synthase inhibition. Future research will include fecal isolate testing, detailed structural elucidation using NMR, and experimental validation to explore the therapeutic potential of Micromonospora-derived compounds."

Journal • Infectious Disease

Queuine: A Bacterial Nucleobase Shaping Translation in Eukaryotes. (PubMed, J Mol Biol) - "This review discusses our current understanding of the cellular and organismal impacts of Q deficiency in eukaryotes. Additionally, it examines recent advancements in technologies for detecting Q modifications at single-base resolution and explores the potential applications of the Q modification system in biotechnology."

Journal • Review • CNS Disorders • Oncology

Queuosine tRNA Modification: Connecting the Microbiome to the Translatome. (PubMed, Bioessays) - "In eukaryotes, queuosine is synthesized by the tRNA-guanine trans-glycosylase (TGT) complex, which incorporates the nucleobase queuine (or Qbase) into guanine of the GUN anticodons...Q's role in neuropsychiatric diseases and cancer is highlighted and discussed. Given the recent interest in Q, and the new findings, more research is needed to fully comprehend its biological function and disease relevance, especially in neurobiology."

Journal • Review • CNS Disorders • Mental Retardation • Oncology • Psychiatry

Exploring the Interactome of the Queuine Salvage Protein DUF2419 in Entamoeba histolytica. (PubMed, Cells) - "Entamoeba histolytica causes amebiasis, a significant global health issue, with millions affected annually, especially in developing countries. The reduction in the EhDUF2419 protein levels was regulated by proteasome-mediated degradation, as evidenced by the reduced degradation in the presence of MG132, a proteasome inhibitor. Our study uncovers the novel interaction of EhDUF2419 with ribosomal proteins and its regulation by the proteasome machinery, providing new insights into its role in E. histolytica and potential therapeutic strategies."

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The utilization of Lysinibacillus bacterial powder to induce Fe plaque formation mitigates cadmium and chromium levels in rice. (PubMed, J Hazard Mater) - "Our findings suggest that Lysinibacillus sp. OR-15 exhibits stable and effective properties as a factor for Cd and Cr adsorb on rice iron plaque, thus mitigating the levels of Cd and Cr in rice grains."

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