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Benzothiadiazole (BTH) regulates grape development, ripening, volatiles, and phenolics. This study used metabolomics and transcriptomics to understand how exogenous BTH affects Chardonnay grapes' maturation and synthesis of isoprenoids. A 0.37 mM BTH solution was sprayed during the swelling and veraison stages, and then the ripe grapes were analyzed. Our results show that BTH application significantly increased levels of important isoprenoids such as free terpinen-4-ol, bound linalool, and 8'-apo-ß-carotenal. Additionally, BTH was found to modulate several signaling pathways, including those involved in ethylene biosynthesis, salicylic acid synthesis, the abscisic acid pathway, and sugar metabolism, by regulating the expression of genes like VvACO4, VvTAR, VvPLD, VvTIP1-1, VvSTKs, VvPK, VvSUC2, VvGST4, and VvSTS. BTH also promoted grapevine resistance by up-regulating the expression of VvHSP20, VvGOLS4, VvOLP, and VvPR-10. Furthermore, BTH affected isoprenoids biosynthesis by regulating the expression of VvTPS35 and VvMYB24. Moreover, 13 hub genes in the MEgreen module were identified as crucial for the biosynthesis of isoprenoids. BTH application during the swelling stage remarkably promoted isoprenoid biosynthesis more effectively than veraison. Our study provides insights into the molecular mechanisms underlying BTH-induced regulation of grape development and offers a promising approach for enhancing the quality and resistance of grapes.

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Introduction: Biofouling poses a significant economic threat to various marine industries, leading to financial losses that can reach billions of euros annually. This study highlights the urgent need for effective alternatives to traditional antifouling agents, particularly following the global ban on organotin compounds. Material and methods: Streptomyces aculeolatus PTM-346 was isolated from sediment samples on the shores of the Madeira Archipelago, Portugal. The crude extract was fractionated using silica flash chromatography and preparative HPLC, resulting in two isolated marinone compounds: madeirone (1), a novel marinone derivative discovered in this study, and neomarinone (2). The antifouling activities of these compounds were tested against five marine bacterial species and the larvae of the mussel Mytilus galloprovincialis. Additionally, in silico and in vivo environmental toxicity evaluations of madeirone (1) and neomarinone (2) were conducted. Results: Madeirone (1) demonstrated significant antibiofilm efficacy, inhibiting Phaeobacter inhibens by up to 66%, Marinobacter hydrocarbonoclasticus by up to 60%, and Cobetia marina by up to 40%. Neomarinone (2) also exhibited substantial antibiofilm activity, with inhibition rates of up to 41% against P. inhibens, 40% against Pseudo-oceanicola batsensis, 56% against M. hydrocarbonoclasticus, 46% against C. marina, and 40% against Micrococcus luteus. The growth inhibition activity at the same concentrations of these compounds remained below 20% for the respective bacteria, highlighting their effectiveness as potent antibiofilm agents without significantly affecting bacterial viability. Additionally, both compounds showed potent effects against the settlement of Mytilus galloprovincialis larvae, with EC50 values of 1.76 µg/mL and 0.12 µg/mL for compounds (1) and (2), respectively, without impairing the viability of the targeted macrofouling species. In silico toxicity predictions and in vivo toxicity assays both support their potential for further development as antifouling agents. Conclusion: The newly discovered metabolite madeirone (1) and neomarinone (2) effectively inhibit both micro- and macrofouling. This distinct capability sets them apart from existing commercial antifouling agents and positions them as promising candidates for biofouling prevention. Consequently, these compounds represent a viable and environmentally friendly alternative for incorporation into paints, primers, varnishes, and sealants, offering significant advantages over traditional copper-based compounds.

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VQ1 and VQ10 are largely unstructured homologous proteins with a significant potential for protein-protein interactions. Yeast two-hybrid (Y2H) analysis confirmed that both proteins interact not only with themselves and each other but also with other VQ and WRKY proteins. Screening an Arabidopsis Y2H library with VQ1 as bait identified 287 interacting proteins. Validation of the screening confirmed that interactions with VQ1 also occurred with VQ10, supporting their functional homology. Although VQ1 or VQ10 proteins do not localize in plastids, 47 VQ1-targets were found to be plastidial proteins. In planta interaction with the isoprenoid biosynthetic enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS) was confirmed by co-immunoprecipitation. DXS oligomerizes through redox-regulated intermolecular disulfide bond formation, and the interaction with VQ1 or VQ10 do not involve their unique C residues. The VQ-DXS protein interaction did not alter plastid DXS localization or its oligomerization state. Although plants with enhanced or reduced VQ1 and VQ10 expression did not exhibit significantly altered levels of isoprenoids compared to wild-type plants, they did display significantly improved or diminished photosynthesis efficiency, respectively.

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Isoprene chemoenzymatic cascades (ICCs) overcome the complexity of natural pathways by leveraging a streamlined two-enzyme cascade, facilitating efficient synthesis of C5-isoprene diphosphate precursors from readily available alcohol derivatives. Despite the documented promiscuity of enzymes in ICCs, exploration of their potential for accessing novel compounds remains limited, and existing methods require additional enzymes for generating longer-chain diphosphates. In this study, we present the utility of Streptococcus mutans undecaprenol kinase (SmUdpK) for the chemoenzymatic synthesis of diverse non-natural isoprenoids. Using a library of 50 synthetic alcohols, we demonstrate that SmUdpK's promiscuity extends to allylic chains as small as four carbons and benzylic alcohols with various substituents. Subsequently, SmUdpK is utilized in an ICC with isopentenyl phosphate kinase and aromatic prenyltransferase to generate multiple non-natural isoprenoids. This work provides evidence that, with proper optimization, SmUdpK can act as the first enzyme in these ICCs, enhancing access to both valuable and novel compounds.

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Background: Several members of the Lamiaceae family of plants produce large amounts of essential oil [EO] that find extensive applications in the food, cosmetics, personal hygiene, and alternative medicine industries. There is interest in enhancing EO metabolism in these plants. Main body: Lavender produces a valuable EO that is highly enriched in monoterpenes, the C10 class of the isoprenoids or terpenoids. In recent years, substantial effort has been made by researchers to study terpene metabolism and enhance lavender EO through plant biotechnology. This paper reviews recent advances related to the cloning of lavender monoterpene biosynthetic genes and metabolic engineering attempts aimed at improving the production of lavender monoterpenes in plants and microbes. Conclusion: Metabolic engineering has led to the improvement of EO quality and yield in several plants, including lavender. Furthermore, several biologically active EO constituents have been produced in microorganisms.

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Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.

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Lipids are a diverse group of compounds that play several important roles in insect physiology. Among biological lipids, the fundamental category comprises fatty acyl structures, with significant members being fatty acids (FAs). They play several crucial functions in insect physiology; they are used as the source of energy for flight and play key roles in the insect immune system. The FAs present in the insect cuticle are known to demonstrate antibacterial and antifungal activity and are considered as potential insecticides. The most abundant family of lipids are the glycerolipids, with numerous cellular functions including storage of energy, structural compartmentation of cells and organelles, and important signaling activities required for regulation of physiological processes (i.e., growth, development, reproduction, diapause, and overwintering). The phospholipids are also highly diversified key components of all cell membranes; they can modify cellular components in response to rapid cold-hardening (RCH), enhancing membrane fluidity and improving survival at low temperatures. The sphingolipids are important structural and signaling bioactive compounds, mostly detected in membranes.Insects are sterol-auxotrophs: they do not have genes, which code enzymes converting farnesyl pyrophosphate to squalene. Similarly, to mammals, the production of steroids in insects is regulated by cytochrome P450 enzymes that convert sterols (mostly cholesterol) to hormonally active steroids. The major molting hormone in insects is 20-hydroxyecdysone, and cholesterol is the required precursor; however, several exemptions from this rule have been noted. This manuscript also reviews the roles of prenol lipids, isoprenoids, lipid vitamins, polyketides, and waxes in the vital processes of insects.

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Pigments serve a multitude of functions in biology including light harvesting for photosynthesis, radiation protection, membrane support, and defense. The ubiquity of pigments-especially within extremophiles found in high-radiation, high-salinity, and dry environments-and their detectability via mission-ready techniques have elevated these molecules as promising targets in the search for evidence of life elsewhere. Moreover, the detection of pigments has been proposed as a "smoking gun" for extraterrestrial life as it has been suggested that these molecules cannot be generated abiotically. However, while pigments may hold promise as a biosignature, current understanding of their possible prebiotic origins remains understudied and uncertain. Better understanding of the abiotic synthesis of pigments is critical for evaluating the biogenicity of any pigment detected during missions, including by the Mars Perseverance rover or from returned samples. Compounding this uncertainty is the broad definition of pigment as it includes any compound capable of absorbing visible light and by itself does not specify a particular chemical motif. While not experimentally verified, there are promising prebiotic routes for generating pigments including hemes, chlorophylls, and carotenoids. Herein, we review the biochemistry of pigments, the inherent assumptions made when searching for these molecules in the field, their abiotic synthesis in industry and prebiotic reactions, prebiotically relevant molecules that can mimic their spectral signatures, and implications/recommendations for future work.

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Isoprenoids and their derivatives, essential for all cellular life on Earth, are particularly crucial in archaeal membrane lipids, suggesting that their biosynthesis pathways have ancient origins and play pivotal roles in the evolution of early life. Despite all eukaryotes, archaea, and a few bacterial lineages being known to exclusively use the mevalonate (MVA) pathway to synthesize isoprenoids, the origin and evolutionary trajectory of the MVA pathway remain controversial. Here, we conducted a thorough comparison and phylogenetic analysis of key enzymes across the four types of MVA pathway, with the particular inclusion of metagenome assembled genomes (MAGs) from uncultivated archaea. Our findings support an archaeal origin of the MVA pathway, likely postdating the divergence of Bacteria and Archaea from the Last Universal Common Ancestor (LUCA), thus implying the LUCA's enzymatic inability for isoprenoid biosynthesis. Notably, the Asgard archaea are implicated in playing central roles in the evolution of the MVA pathway, serving not only as putative ancestors of the eukaryote- and Thermoplasma-type routes, but also as crucial mediators in the gene transfer to eukaryotes, possibly during eukaryogenesis. Overall, this study advances our understanding of the origin and evolutionary history of the MVA pathway, providing unique insights into the lipid divide and the evolution of early life.

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Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

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The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismal levels. Two integral membrane proteins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and Scap, are key targets of a complex feedback regulatory system that operates to ensure cholesterol homeostasis. HMGCR catalyzes the rate-limiting step in the transformation of the 2-carbon precursor acetate to 27-carbon cholesterol. Scap mediates proteolytic activation of sterol regulatory element-binding protein-2 (SREBP-2), a membrane-bound transcription factor that controls expression of genes involved in the synthesis and uptake of cholesterol. Sterol accumulation triggers binding of HMGCR to endoplasmic reticulum (ER)-localized Insig proteins, leading to the enzyme's ubiquitination and proteasome-mediated ER-associated degradation (ERAD). Sterols also induce binding of Insigs to Scap, which leads to sequestration of Scap and its bound SREBP-2 in the ER, thereby preventing proteolytic activation of SREBP-2 in the Golgi. The oxygenated cholesterol derivative 25-hydroxycholesterol (25HC) and the methylated cholesterol synthesis intermediate 24,25-dihydrolanosterol (DHL) differentially modulate HMGCR and Scap. While both sterols promote binding of HMGCR to Insigs for ubiquitination and subsequent ERAD, only 25HC inhibits the Scap-mediated proteolytic activation of SREBP-2. We showed previously that 1,1-bisphosphonate esters mimic DHL, accelerating ERAD of HMGCR while sparing SREBP-2 activation. Building on these results, our current studies reveal specific, Insig-independent photoaffinity labeling of HMGCR by photoactivatable derivatives of the 1,1-bisphosphonate ester SRP-3042 and 25HC. These findings disclose a direct sterol binding mechanism as the trigger that initiates the HMGCR ERAD pathway, providing valuable insights into the intricate mechanisms that govern cholesterol homeostasis.

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As the source of isoprenoid precursors, the plastidial methylerythritol phosphate (MEP) pathway plays an essential role in plant development. Here, we report a novel rice (Oryza sativa L.) mutant ygl3 (yellow-green leaf3) that exhibits yellow-green leaves and lower photosynthetic efficiency compared to the wild type due to abnormal chloroplast ultrastructure and reduced chlorophyll content. Map-based cloning showed that YGL3, one of the major genes involved in the MEP pathway, encodes 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, which is localized in the thylakoid membrane. A single base substitution in ygl3 plants resulted in lower 4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity and lower contents of isopentenyl diphosphate (IPP) compared to the wild type. The transcript levels of genes involved in the syntheses of chlorophyll and thylakoid membrane proteins were significantly reduced in the ygl3 mutant compared to the wild type. The phytochrome interacting factor-like gene OsPIL11 regulated chlorophyll synthesis during the de-etiolation process by directly binding to the promoter of YGL3 to activate its expression. The findings provides a theoretical basis for understanding the molecular mechanisms by which the MEP pathway regulate chloroplast development in rice.

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The enzymology of the key steps in the archaeal phospholipid biosynthetic pathway has been elucidated in recent years. In contrast, the complete biosynthetic pathways for proposed membrane regulators consisting of polyterpenes, such as carotenoids, respiratory quinones, and polyprenols remain unknown. Notably, the multiplicity of geranylgeranyl reductases (GGRs) in archaeal genomes has been correlated with the saturation of polyterpenes. Although GGRs, which are responsible for saturation of the isoprene chains of phospholipids, have been identified and studied in detail, there is little information regarding the structure and function of the paralogs. Here, we discuss the diversity of archaeal membrane-associated polyterpenes which is correlated with the genomic loci, structural and sequence-based analyses of GGR paralogs.

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Isoprenoid biosynthesis has a significant requirement for the co-factor NADPH. Thus, increasing NADPH levels for enhancing isoprenoid yields in synthetic biology is critical. Previous efforts have focused on diverting flux into the pentose phosphate pathway or overproducing enzymes that generate NADPH. In this study, we instead focused on increasing the efficiency of enzymes that generate NADPH. We first established a robust genetic screen that allowed us to screen improved variants. The pentose phosphate pathway enzyme, glucose 6-phosphate dehydrogenase (G6PD), was chosen for further improvement. Different gene fusions of G6PD with the downstream enzyme in the pentose phosphate pathway, 6-phosphogluconolactonase (6PGL), were created. The linker-less G6PD-6PGL fusion displayed the highest activity, and although it had slightly lower activity than the WT enzyme, the affinity for G6P was higher and showed higher yields of the diterpenoid sclareol in vivo. A second gene fusion approach was to fuse G6PD to truncated HMG-CoA reductase, the rate-limiting step and also the major NADPH consumer in the pathway. Both domains were functional, and the fusion also yielded higher sclareol levels. We simultaneously carried out a rational mutagenesis approach with G6PD, which led to the identification of two mutants of G6PD, N403D and S238QI239F, that showed 15-25% higher activity in vitro. The diterpene sclareol yields were also increased in the strains overexpressing these mutants relative to WT G6PD, and these will be very beneficial in synthetic biology applications.

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Due to global climate change, drought is emerging as a major threat to plant growth and agricultural productivity. Abscisic acid (ABA) has been implicated in plant drought tolerance, however, its retarding effects on plant growth cannot be ignored. The reactions catalyzed by 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) proteins are critical steps within the isoprenoid biosynthesis in plants. Here, five DXS (CtDXS1-5) and two DXR (CtDXR1-2) genes were identified from Cassia tora genome. Based on multiple assays including the phylogeny, cis-acting element, expression pattern, and subcellular localization, CtDXS1 and CtDXR1 genes might be potential candidates controlling the isoprenoid biosynthesis. Intriguingly, CtDXS1 transgenic plants resulted in drought tolerance but retardant growth, while CtDXR1 transgenic plants exhibited both enhanced drought tolerance and increased growth. By comparison of ß-carotene, chlorophyll, abscisic acid (ABA) and gibberellin 3 (GA3) contents in wild-type and transgenic plants, the absolute contents and (or) altered GA3/ABA levels were suggested to be responsible for the balance between drought tolerance and plant growth. The transcriptome of CtDXR1 transgenic plants suggested that the transcript levels of key genes, such as DXS, 9-cis-epoxycarotenoid dioxygenases (NCED), ent-kaurene synthase (KS) and etc, involved with chlorophyll, ß-carotene, ABA and GA3 biosynthesis were induced and their contents increased accordingly. Collectively, the trade-off effect induced by CtDXR1 was associated with redesigning architecture in phytohormone homeostasis and thus was highlighted for future breeding purposes.

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Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low molecular weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plants cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, carotenoids, tocopherol (vitamin E), ubiquinone, and plastoquinone. Their functioning and their reactivity with respect to individual ROS will be described. This review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow various plant lines with given properties to be obtained in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of biosynthesis and the content of these antioxidants are discussed.

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Globally, due to widespread dispersion, intraspecific diversity, and crucial ecological components of halophilic ecosystems, halophilic bacteria is considered one of the key models for ecological, adaptative, and biotechnological applications research in saline environments. With this aim, the present study was to enlighten the plant growth-promoting features and investigate the systematic genome of a halophilic bacteria, Virgibacillus halodenitrificans ASH15, through single-molecule real-time (SMRT) sequencing technology. Results showed that strain ASH15 could survive in high salinity up to 25% (w/v) NaCl concentration and express plant growth-promoting traits such as nitrogen fixation, plant growth hormones, and hydrolytic enzymes, which sustain salt stress. The results of pot experiment revealed that strain ASH15 significantly enhanced sugarcane plant growth (root shoot length and weight) under salt stress conditions. Moreover, the sequencing analysis of the strain ASH15 genome exhibited that this strain contained a circular chromosome of 3,832,903 bp with an average G+C content of 37.54%: 3721 predicted protein-coding sequences (CDSs), 24 rRNA genes, and 62 tRNA genes. Genome analysis revealed that the genes related to the synthesis and transport of compatible solutes (glycine, betaine, ectoine, hydroxyectoine, and glutamate) confirm salt stress as well as heavy metal resistance. Furthermore, functional annotation showed that the strain ASH15 encodes genes for root colonization, biofilm formation, phytohormone IAA production, nitrogen fixation, phosphate metabolism, and siderophore production, which are beneficial for plant growth promotion. Strain ASH15 also has a gene resistance to antibiotics and pathogens. In addition, analysis also revealed that the genome strain ASH15 has insertion sequences and CRISPRs, which suggest its ability to acquire new genes through horizontal gene transfer and acquire immunity to the attack of viruses. This work provides knowledge of the mechanism through which V. halodenitrificans ASH15 tolerates salt stress. Deep genome analysis, identified MVA pathway involved in biosynthesis of isoprenoids, more precisely "Squalene." Squalene has various applications, such as an antioxidant, anti-cancer agent, anti-aging agent, hemopreventive agent, anti-bacterial agent, adjuvant for vaccines and drug carriers, and detoxifier. Our findings indicated that strain ASH15 has enormous potential in industries such as in agriculture, pharmaceuticals, cosmetics, and food.

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Introduction: Plant growth and greening in response to light require the synthesis of photosynthetic pigments such as chlorophylls and carotenoids, which are derived from isoprenoid precursors. In Arabidopsis, the pseudo-etiolated-in-light phenotype is caused by the overexpression of repressor of photosynthetic genes 2 (RPGE2), which regulates chlorophyll synthesis and photosynthetic genes. Methods: We investigated a homologous protein in the Russian dandelion (Taraxacum koksaghyz) to determine its influence on the rich isoprenoid network in this species, using a combination of in silico analysis, gene overexpression, transcriptomics and metabolic profiling. Results: Homology-based screening revealed a gene designated pseudo-etiolated-in-light-like (TkPEL-like), and in silico analysis identified a light-responsive G-box element in its promoter. TkPEL-like overexpression in dandelion plants and other systems reduced the levels of chlorophylls and carotenoids, but this was ameliorated by the mutation of one or both conserved cysteine residues. Comparative transcriptomics in dandelions overexpressing TkPEL-like showed that genes responsible for the synthesis of isoprenoid precursors and chlorophyll were downregulated, probably explaining the observed pale green leaf phenotype. In contrast, genes responsible for carotenoid synthesis were upregulated, possibly in response to feedback signaling. The evaluation of additional differentially expressed genes revealed interactions between pathways. Discussion: We propose that TkPEL-like negatively regulates chlorophyll- and photosynthesis-related genes in a light-dependent manner, which appears to be conserved across species. Our data will inform future studies addressing the regulation of leaf isoprenoid biosynthesis and photomorphogenesis and could be used in future breeding strategies to optimize selected plant isoprenoid profiles and generate suitable plant-based production platforms.

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BACKGROUND: Farnesol (FOL) prevents the onset of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). OBJECTIVE: We examined the transcriptomic profile of the brains of EAE mice treated with daily oral FOL using next-generation sequencing (RNA-seq). METHODS: Transcriptomics from whole brains of treated and untreated EAE mice at the peak of EAE was performed. RESULTS: EAE-induced mice, compared to naïve, healthy mice, overall showed increased expression in pathways for immune response, as well as an increased cytokine signaling pathway, with downregulation of cellular stress proteins. FOL downregulates pro-inflammatory pathways and attenuates the immune response in EAE. FOL downregulated the expression of genes involved in misfolded protein response, MAPK activation/signaling, and pro-inflammatory response. CONCLUSION: This study provides insight into the molecular impact of FOL in the brain and identifies potential therapeutic targets of the isoprenoid pathway in MS patients.

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Sea ice plays a fundamental role in Arctic marine environments, by driving primary productivity and sustaining ice-associated ecosystems. Simultaneously, sea ice influences the contamination of Arctic marine organisms, by modifying contaminant cycles or their bioavailability. Changes in sea ice conditions could therefore profoundly impact the functioning of Arctic marine food webs and their contamination. Top predators such as seabirds, which are subject to bioaccumulation and biomagnification of contaminants, are particularly exposed. In this context, the present study aims to investigate the influence of sea ice and of the use of ice-derived resources on the contamination of seabirds by mercury (Hg). To this end, eggs of thick-billed murres (Brünnich's guillemots, Uria lomvia; n = 60) were collected on Prince Leopold Island (Canadian High Arctic) during four years of varying ice conditions (2010-2013). Trophic tracers (i.e., Highly Branched Isoprenoids, HBIs - an indicator of the use of ice-derived resources; carbon and nitrogen stable isotopes - indicators of foraging habitats and trophic status), as well as total Hg concentrations were quantified. Results showed that feeding on ice-derived resources (as indicated by HBI concentrations) was positively correlated to sea ice cover, and both positively influenced Hg concentrations in murre eggs. However, when testing for the best predictor with model selection, sea ice concentration only drove Hg contamination in murres. This work provides new insights into the role of sea ice and ice-derived resources in the contamination by Hg of Arctic wildlife. Further research is now needed to better understand the relationship between sea ice and Hg contamination in Arctic biota and its underlying mechanisms, but also to identify Hg sources in rapidly changing environmental conditions in the Arctic.

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