PubMed

Mol Nutr Food Res. 2023 Sep 6:e2300052. doi: 10.1002/mnfr.202300052. Online ahead of print.ABSTRACTSCOPE: Although many beneficial health effects are attributed to polyphenols their influence on the human metabolome has not been elucidated yet. The ubiquitous occurrence of polyphenols in the human diet demands comprehensive knowledge about physiological and toxicological effects of these compounds on human cells.METHODS AND RESULTS: The human hepatocarcinogenic cell line HepG2 is used to elucidate the effects of 13 polyphenols and three respective phenolic degradation products on the human metabolome using HPLC-MS/MS. To investigate structure-activity-relationships, structurally related examples of polyphenols from different compound classes are selected. The analysis of catechins points toward a relation between the degree of hydroxylation and the extent of metabolic effects particularly on the urea cycle and the pentose phosphate pathway (PPP). A correlation between the modulation of the PPP and the stability of the compounds is demonstrated, which may be caused by reactive oxygen species (ROS). The incubation of flavones and alkenylbenzenes demonstrates reduced activity of methoxylated compounds and no impact of the B-ring position.CONCLUSION: In general, polyphenols induce a multitude of metabolic effects, for example, on energy metabolism, PPP, and urea cycle. These metabolic alterations may be related to the widely reported bioactivity of these compounds such as the anticarcinogenic effects.PMID:37672806 | DOI:10.1002/mnfr.202300052

J Nat Prod. 2023 Sep 6. doi: 10.1021/acs.jnatprod.3c00310. Online ahead of print.ABSTRACTThe integration of NMR-metabolomic and genomic analyses can provide enhanced identification of structural properties as well as key biosynthetic information, thus achieving the targeted discovery of new natural products. For this purpose, NMR-based metabolomic profiling of the marine-derived Streptomyces sp. S063 (CGMCC 14582) was performed, by which N-methylated peptides possessing unusual negative 1H NMR chemical shift values were tracked. Meanwhile, genome mining of this strain revealed the presence of an unknown NRPS gene cluster (len) with piperazic-acid-encoding genes (lenE and lenF). Under the guidance of the combined information, two cyclic decapeptides, lenziamides D1 (1) and B1 (2), were isolated from Streptomyces sp. S063, which contains piperazic acids with negative 1H NMR values. The structures of 1 and 2 were determined by extensive spectroscopic analysis combined with Marfey's method and ECD calculations. Furthermore, we provided a detailed model of lenziamide (1 and 2) biosynthesis in Streptomyces sp. S063. In the cytotoxicity evaluation, 1 and 2 showed moderate growth inhibition against the human cancer cells HEL, H1975, H1299, and drug-resistant A549-taxol with IC50 values of 8-24 μM.PMID:37672645 | DOI:10.1021/acs.jnatprod.3c00310

Sci Adv. 2023 Sep 8;9(36):eadh2023. doi: 10.1126/sciadv.adh2023. Epub 2023 Sep 6.ABSTRACTPrevious studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline incorporation into proteins was lower in detached cells compared to other amino acids, there was an increased production of the proline-rich protein collagen. The increased excretion of proline from detached cells was also shown to be used by macrophages, an abundant and important component of the tumor microenvironment. Our study suggests that detachment induced accumulation and secretion of proline may contribute to tumor progression by supporting increased production of extracellular matrix and providing proline to surrounding stromal cells.PMID:37672588 | DOI:10.1126/sciadv.adh2023

J Mol Med (Berl). 2023 Sep 6. doi: 10.1007/s00109-023-02362-z. Online ahead of print.ABSTRACTInvestigating the cross talk of different omics layers is crucial to understand molecular pathomechanisms of metabolic diseases like obesity. Here, we present a large-scale association meta-analysis of genome-wide whole blood and peripheral blood mononuclear cell (PBMC) gene expressions profiled with Illumina HT12v4 microarrays and metabolite measurements from dried blood spots (DBS) characterized by targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) in three large German cohort studies with up to 7706 samples. We found 37,295 associations comprising 72 amino acids (AA) and acylcarnitine (AC) metabolites (including ratios) and 8579 transcripts. We applied this catalogue of associations to investigate the impact of associating transcript-metabolite pairs on body mass index (BMI) as an example metabolic trait. This is achieved by conducting a comprehensive mediation analysis considering metabolites as mediators of gene expression effects and vice versa. We discovered large mediation networks comprising 27,023 potential mediation effects within 20,507 transcript-metabolite pairs. Resulting networks of highly connected (hub) transcripts and metabolites were leveraged to gain mechanistic insights into metabolic signaling pathways. In conclusion, here, we present the largest available multi-omics integration of genome-wide transcriptome data and metabolite data of amino acid and fatty acid metabolism and further leverage these findings to characterize potential mediation effects towards BMI proposing candidate mechanisms of obesity and related metabolic diseases. KEY MESSAGES: Thousands of associations of 72 amino acid and acylcarnitine metabolites and 8579 genes expand the knowledge of metabolome-transcriptome associations. A mediation analysis of effects on body mass index revealed large mediation networks of thousands of obesity-related gene-metabolite pairs. Highly connected, potentially mediating hub genes and metabolites enabled insight into obesity and related metabolic disease pathomechanisms.PMID:37672078 | DOI:10.1007/s00109-023-02362-z

Expert Rev Mol Diagn. 2023 Sep 6:1-12. doi: 10.1080/14737159.2023.2254884. Online ahead of print.ABSTRACTBACKGROUND: Aberrant methylation and metabolic perturbations may deepen our understanding of hepatocarcinogenesis and help identify novel biomarkers for diagnosing hepatocellular carcinoma (HCC). We aimed to develop an HCC model based on a multi-omics.RESEARCH DESIGN AND METHODS: Four hundred patient samples (200 with HCC and 200 with hepatitis B virus-related liver disease (HBVLD)) were subjected to liquid chromatography-mass spectrometry and multiplex bisulfite sequencing. Integrative analysis of clinical data, CpG data, and metabolome for the 20 complete imputation datasets within a for-loopwas used to identify biomarker.RESULTS: Totally, 1,140 metabolites were annotated, of which 125 were differentially expressed. Lipid metabolism reprogramming in HCC, resulting in phosphatidylcholines (PC) significantly downregulated, partly due to the altered mitochondrial beta-oxidation of fatty acids with diverse chain lengths. Age, sex, serum-fetoprotein levels, cg05166871,cg14171514, cg18772205, PC (O-16:0/20:3(8Z, 11Z, 14Z)), and PC (16:1(9Z)/P-18:0) were used to develop the HCC model. The model presented a good diagnostic and an acceptable predictive performance. The cumulative incidence of HCC in low- and high-risk groups of HBVLD patients were 1.19% and 21.40%, respectively (p = 0.0039).CONCLUSIONS: PCs serve as potential plasma biomarkers and help identify patients with HBVLD at risk of HCC who should be screened for early diagnosis and intervention.PMID:37672012 | DOI:10.1080/14737159.2023.2254884

Gut Microbes. 2023 Dec;15(2):2252764. doi: 10.1080/19490976.2023.2252764.ABSTRACTThe microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.PMID:37671803 | DOI:10.1080/19490976.2023.2252764

Hum Reprod. 2023 Sep 6:dead177. doi: 10.1093/humrep/dead177. Online ahead of print.ABSTRACTSTUDY QUESTION: Are human ovarian aging and the age-related female fertility decline caused by oxidative stress and mitochondrial dysfunction in oocytes?SUMMARY ANSWER: We found oxidative damage in oocytes of advanced maternal age, even at the primordial follicle stage, and confirmed mitochondrial dysfunction in such oocytes, which likely resulted in the use of alternative energy sources.WHAT IS KNOWN ALREADY: Signs of reactive oxygen species-induced damage and mitochondrial dysfunction have been observed in maturing follicles, and even in early stages of embryogenesis. However, although recent evidence indicates that also primordial follicles have metabolically active mitochondria, it is still often assumed that these follicles avoid oxidative phosphorylation to prevent oxidative damage in dictyate arrested oocytes. Data on the influence of ovarian aging on oocyte metabolism and mitochondrial function are still limited.STUDY DESIGN, SIZE, DURATION: A set of 39 formalin-fixed and paraffin-embedded ovarian tissue biopsies were divided into different age groups and used for immunofluorescence analysis of oxidative phosphorylation activity and oxidative damage to proteins, lipids, and DNA. Additionally, 150 immature oocytes (90 germinal vesicle oocytes and 60 metaphase I oocytes) and 15 cumulus cell samples were divided into different age groups and used for targeted metabolomics and lipidomics analysis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissues used for immunofluorescence microscopy were collected through PALGA, the nationwide network, and registry of histo- and cytopathology in The Netherlands. Comprehensive metabolomics and lipidomics were performed by liquid-liquid extraction and full-scan mass spectrometry, using oocytes and cumulus cells of women undergoing ICSI treatment based on male or tubal factor infertility, or fertility preservation for non-medical reasons.MAIN RESULTS AND THE ROLE OF CHANCE: Immunofluorescence imaging on human ovarian tissue indicated oxidative damage by protein and lipid (per)oxidation already at the primordial follicle stage. Metabolomics and lipidomics analysis of oocytes and cumulus cells in advanced maternal-age groups demonstrated a shift in the glutathione-to-oxiglutathione ratio and depletion of phospholipids. Age-related changes in polar metabolites suggested a decrease in mitochondrial function, as demonstrated by NAD+, purine, and pyrimidine depletion, while glycolysis substrates and glutamine accumulated, with age. Oocytes from women of advanced maternal age appeared to use alternative energy sources like glycolysis and the adenosine salvage pathway, and possibly ATP which showed increased production in cumulus cells.LIMITATIONS, REASONS FOR CAUTION: The immature oocytes used in this study were all subjected to ovarian stimulation with high doses of follicle-stimulating hormones, which might have concealed some age-related differences.WIDER IMPLICATIONS OF THE FINDINGS: Further studies on how to improve mitochondrial function, or lower oxidative damage, in oocytes from women of advanced maternal age, for instance by supplementation of NAD+ precursors to promote mitochondrial biogenesis, are warranted. In addition, supplementing the embryo medium of advanced maternal-age embryos with such compounds could be a treatment option worth exploring.STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Amsterdam UMC. The authors declare to have no competing interests.TRIAL REGISTRATION NUMBER: N/A.PMID:37671592 | DOI:10.1093/humrep/dead177

PeerJ. 2023 Sep 1;11:e15856. doi: 10.7717/peerj.15856. eCollection 2023.ABSTRACTBACKGROUND: Ambient fine particulate matter ≤ 2.5 µm (PM2.5) air pollution exposure has been identified as a global health threat, the epidemiological evidence suggests that PM2.5 increased the risk of chronic kidney disease (CKD) among the diabetes mellitus (DM) patients. Despite the growing body of research on PM2.5 exposure, there has been limited investigation into its impact on the kidneys and the underlying mechanisms. Past studies have demonstrated that PM2.5 exposure can lead to lipid metabolism disorder, which has been linked to the development and progression of diabetic kidney disease (DKD).METHODS: In this study, db/db mice were exposed to different dosage PM2.5 for 8 weeks. The effect of PM2.5 exposure was analysis by assessment of renal function, pathological staining, immunohistochemical (IHC), quantitative real-time PCR (qPCR) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) based metabolomic analyses.RESULTS: The increasing of Oil Red staining area and adipose differentiation related protein (ADRP) expression detected by IHC staining indicated more ectopic lipid accumulation in kidney after PM2.5 exposure, and the increasing of SREBP-1 and the declining of ATGL detected by IHC staining and qPCR indicated the disorder of lipid synthesisandlipolysis in DKD mice kidney after PM2.5 exposure. The expressions of high mobility group nucleosome binding protein 1 (HMGN1) and kidney injury molecule 1 (KIM-1) that are associated with kidney damage increased in kidney after PM2.5 exposure. Correlation analysis indicated that there was a relationship between HMGN1-KIM-1 and lipid metabolic markers. In addition, kidneys of mice were analyzed using LC-MS/MS based metabolomic analyses. PM2.5 exposure altered metabolic profiles in the mice kidney, including 50 metabolites. In conclusion the results of this study show that PM2.5 exposure lead to abnormal renal function and further promotes renal injury by disturbance of renal lipid metabolism and alter metabolic profiles.PMID:37671359 | PMC:PMC10476618 | DOI:10.7717/peerj.15856

PeerJ. 2023 Sep 1;11:e16034. doi: 10.7717/peerj.16034. eCollection 2023.ABSTRACTOBJECTIVE: The classification and clinical usage of the different species of bead ginseng are often confused. Therefore, we conducted an integrated metabolomics and transcriptome analysis of three main species of Panax, including Panax japonicas, Panax pseudoginseng, and Panax pseudo-ginseng var. elegantior.METHODS: A broad metabolome and transcriptome analysis for three origins of bead ginseng plants was performed using UPLC-ESI-MS/MS, RNA sequencing and annotation, and bioinformatic analysis of transcriptome data.RESULTS: The levels of 830 metabolites were determined. A total of 291 differentially accumulated metabolites (DAMs) between Panax pseudo-ginseng var. elegantior and Panax japonicas (Group A), with 73 upregulated and 218 downregulated. A total of 331 DAMs (110 upregulated and 221 downregulated) were found between Panax pseudoginseng and Panax japonicas (group B). There were 160 DAMs (102 up-regulated and 58 down-regulated) between Panax pseudoginseng and Panax pseudo-ginseng var. elegantior (group C). In addition, RNA sequencing was performed in the above three ways. A total of 16,074 differential expression genes (DEGs) were detected between Group A, in which 7,723 genes were upregulated and 8,351 genes were downregulated by RNA sequencing. Similarly, 15,705 genes were differentially expressed between group B, in which 7,436 genes were upregulated and 8,269 genes were downregulated. However, only 1,294 genes were differentially expressed between group C, in which 531 genes were upregulated and 763 genes were downregulated. We performed differential gene analysis on three groups of samples according to the Venn diagram and found that 181 differential genes were present. A total of 3,698 and 2,834 unique genes were in groups A and B, while 130 unique genes were in group C.CONCLUSIONS: This study provides metabolome and transcriptome information for three bead ginseng plants. The analysis of the metabolite content showed differences in the attributes of the three bead ginseng, contained mainly flavonoids, phenolic acids as well as terpenes.PMID:37671355 | PMC:PMC10476608 | DOI:10.7717/peerj.16034

Cureus. 2023 Aug 5;15(8):e42985. doi: 10.7759/cureus.42985. eCollection 2023 Aug.ABSTRACTBackground Basal, reflex, and emotional tears differ in chemical components. It is not yet known whether chemical differences exist in tears of different emotions. We investigated the biochemical basis of emotional tears by performing non-targeted metabolomics analyses of positive and negative emotional tears of humans. Methods Samples of reflex, negative, and positive emotional tears were obtained from 12 healthy college participants (11 females and one male). Untargeted metabolomics was performed to identify metabolites in different types of tears. The differentially altered metabolites were screened and assessed using univariate and multivariate analyses. Results The orthogonal partial least squares discriminant analysis model showed that reflex, negative, and positive emotional tears were clearly separated. A total of 133 significantly differentially expressed metabolites of electrospray ionization source (ESI-) mode were identified between negative and positive emotional tears. The top 50 differentially expressed metabolites between negative and positive emotional tears were highly correlated. Pathway analysis revealed that secretion of negative emotional tears was associated with some synapses in the brain, regulation of a series of endocrine hormones, including the estrogen signaling pathway, and inflammation activities, while secretion of positive emotional tears was correlated with biotin and caffeine metabolism. Conclusions It is indicated that metabolic profiles of reflex, positive, and negative emotional tears of humans are distinct, and secretion of the tears involves distinct biological activities. Therefore, we present a chemical method for detecting human emotions, which may become a powerful tool for the diagnosis of mental diseases and the identification of fake tears.PMID:37671209 | PMC:PMC10476548 | DOI:10.7759/cureus.42985

Open Life Sci. 2023 Aug 31;18(1):20220708. doi: 10.1515/biol-2022-0708. eCollection 2023.ABSTRACTNucleosides, organic acids, and amino acids separated from Morchella esculenta are well known for their nutritional value and flavor. However, how to increase their content in a better way has been a challenge. In this study, the effect of adding jujube kernel on the active components of M. esculenta was investigated by untargeted metabolomics using UPLC-MS/MS. A total of 1,243 metabolites were identified, of which 262 metabolites (21.078%) were organic acids and derivatives, 245 metabolites (19.71%) were lipids and lipid-like molecules, and 26 metabolites (2.092%) were nucleosides, nucleotides, and analogues. Subsequently, differential metabolites between groups were screened by the orthogonal partial least squares-discriminant analysis model, which showed that 256 metabolites were identified as significantly different for the positive ion model and 149 for the negative ion model. Moreover, significant differential metabolites (VIP > 1, P < 0.05) in annotation of kyoto encyclopedia of genes and genomes pathway were investigated, which showed that ABC transporters were the most commonly observed transporters, followed by pyrimidine metabolism and purine metabolism. The results indicated that the main components of jujube kernel might be conducive to the accumulation of nucleoside organic acids and amino acid metabolites in M. esculenta. These results provide important information for the understanding of more suitable way for cultivation of M. esculenta.PMID:37671097 | PMC:PMC10476485 | DOI:10.1515/biol-2022-0708

Cell Rep Methods. 2023 Jul 26;3(8):100539. doi: 10.1016/j.crmeth.2023.100539. eCollection 2023 Aug 28.ABSTRACTThe metabolic "handshake" between the microbiota and its mammalian host is a complex, dynamic process with major influences on health. Dissecting the interaction between microbial species and metabolites found in host tissues has been a challenge due to the requirement for invasive sampling. Here, we demonstrate that secondary electrospray ionization-mass spectrometry (SESI-MS) can be used to non-invasively monitor metabolic activity of the intestinal microbiome of a live, awake mouse. By comparing the headspace metabolome of individual gut bacterial culture with the "volatilome" (metabolites released to the atmosphere) of gnotobiotic mice, we demonstrate that the volatilome is characteristic of the dominant colonizing bacteria. Combining SESI-MS with feeding heavy-isotope-labeled microbiota-accessible sugars reveals the presence of microbial cross-feeding within the animal intestine. The microbiota is, therefore, a major contributor to the volatilome of a living animal, and it is possible to capture inter-species interaction within the gut microbiota using volatilome monitoring.PMID:37671025 | PMC:PMC10475793 | DOI:10.1016/j.crmeth.2023.100539

Front Endocrinol (Lausanne). 2023 Aug 21;14:1180415. doi: 10.3389/fendo.2023.1180415. eCollection 2023.ABSTRACTBACKGROUND AND PURPOSE: Nonproliferative diabetic retinopathy (NPDR) occurs in the early stages of Diabetic retinopathy (DR), and the study of its metabolic markers will help to prevent DR. Hence, we aimed to establish a risk score based on multiple metabolites through untargeted metabolomic analysis of venous blood from NPDR patients and diabetic non-DR patients.EXPERIMENTAL APPROACH: Untargeted metabolomics of venous blood samples from patients with NPDR, diabetes melitus without DR were performed using high-performance liquid chromatography-mass spectrometry.RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites in plasma samples from patients with NPDR and diabetic non-DR patients. NPDR patients had significantly higher levels of phenylacetylglycine, L-aspartic acid, tiglylglycine, and 3-sulfinato-L-alaninate, and lower level of indolelactic acid, threonic acid, L-arginine (Arg), and 4-dodecylbenzenesulfonic acid compared to control. The expression profiles of these eight NPDR risk-related characteristic metabolites were analyzed using Cox regression to establish a risk score model. Subsequently, univariate and multivariate Cox regression analyses were used to determine that this risk score model was a predictor of independent prognosis for NPDR.CONCLUSIONS: Untargeted metabolome analysis of blood metabolites revealed unreported metabolic alterations in NPDR patients compared with those in diabetic non-DR patients or MH. In the venous blood, we identified depleted metabolites thA and Arg, indicating that they might play a role in NPDR development.PMID:37670880 | PMC:PMC10476524 | DOI:10.3389/fendo.2023.1180415

Front Plant Sci. 2023 Aug 21;14:1247913. doi: 10.3389/fpls.2023.1247913. eCollection 2023.NO ABSTRACTPMID:37670867 | PMC:PMC10476098 | DOI:10.3389/fpls.2023.1247913

Front Plant Sci. 2023 Aug 21;14:1273010. doi: 10.3389/fpls.2023.1273010. eCollection 2023.NO ABSTRACTPMID:37670864 | PMC:PMC10476088 | DOI:10.3389/fpls.2023.1273010

iScience. 2023 Aug 14;26(9):107619. doi: 10.1016/j.isci.2023.107619. eCollection 2023 Sep 15.ABSTRACTIgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.PMID:37670790 | PMC:PMC10475480 | DOI:10.1016/j.isci.2023.107619

Zhonghua Bing Li Xue Za Zhi. 2023 Sep 8;52(9):981-984. doi: 10.3760/cma.j.cn112151-20221202-01019.ABSTRACT空间代谢组学是基于质谱成像技术，对组织中代谢物的种类、含量、空间分布差异进行分析，具有无需标记、免基质、灵敏度高的特点，相比传统代谢组学增加了对空间信息的研究。本文介绍代谢组学和质谱成像技术以及它们的研究现状，重点综述空间代谢组学在肿瘤各个领域的应用，介绍了空间代谢组学技术的现有瓶颈并展望了其未来发展方向。.PMID:37670638 | DOI:10.3760/cma.j.cn112151-20221202-01019

Nucleic Acids Res. 2023 Sep 6:gkad725. doi: 10.1093/nar/gkad725. Online ahead of print.ABSTRACTTranslational fidelity is critical for microbial fitness, survival and stress responses. Much remains unknown about the genetic and environmental control of translational fidelity and its single-cell heterogeneity. In this study, we used a high-throughput fluorescence-based assay to screen a knock-out library of Escherichia coli and identified over 20 genes critical for stop-codon readthrough. Most of these identified genes were not previously known to affect translational fidelity. Intriguingly, we show that several genes controlling metabolism, including cyaA and crp, enhance stop-codon readthrough. CyaA catalyzes the synthesis of cyclic adenosine monophosphate (cAMP). Combining RNA sequencing, metabolomics and biochemical analyses, we show that deleting cyaA impairs amino acid catabolism and production of ATP, thus repressing the transcription of rRNAs and tRNAs to decrease readthrough. Single-cell analyses further show that cAMP is a major driver of heterogeneity in stop-codon readthrough and rRNA expression. Our results highlight that carbon metabolism is tightly coupled with stop-codon readthrough.PMID:37670559 | DOI:10.1093/nar/gkad725

Proteomics. 2023 Sep 5:e2300032. doi: 10.1002/pmic.202300032. Online ahead of print.ABSTRACTMetabolomics, the systematic measurement of small molecules (<1000 Da) in a given biological sample, is a fast-growing field with many different applications. In contrast to transcriptomics and proteomics, sharing of data is not as widespread in metabolomics, though more scientists are sharing their data nowadays. However, to improve data analysis tools and develop new data analytical approaches and to improve metabolite annotation and identification, sharing of reference data is crucial. Here, different possibilities to share (metabolomics) data are reviewed and some recent approaches and applications regarding the (re-)use and (re-)analysis are highlighted.PMID:37670538 | DOI:10.1002/pmic.202300032

Clin Transl Med. 2023 Sep;13(9):e1392. doi: 10.1002/ctm2.1392.NO ABSTRACTPMID:37670478 | DOI:10.1002/ctm2.1392