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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Novosphingobium aromaticivorans LigR coordinates transcription of genes involved in metabolism of multiple types of aromatics

Aromatic compounds are a ubiquitous and diverse family of chemicals with functions as biomolecules, natural products, industrial chemicals, and pollutants. Novosphingobium aromaticivorans DSM 12444 uses multiple inducible pathways to catabolize H-, G-, and S-type aromatics that contain zero, one, or two methoxy groups, respectively. Here, we obtain a systems-level view of the transcriptional control of its aromatic metabolic pathways. Several in vitro analyses found that a N. aromaticivorans homolog of the Sphingobium lignivorans SYK-6 transcription factor LigR bound genomic DNA upstream of genes involved in metabolism of multiple aromatic types. We found that a ΔLigR mutant had growth defects on all three types of aromatics as sole carbon sources. Transcriptomic analysis revealed that LigR was required to increase expression of gene products that function in metabolism of all three aromatic types. We also found that, in media containing both glucose and an aromatic carbon source, the ΔLigR mutant directed intermediates through alternative aromatic metabolic pathways. Protein-DNA binding assays showed that N. aromaticivorans LigR binds immediately upstream of promoters of genes involved in aromatic metabolism. We found that N. aromaticivorans LigR coordinates the expression of enzymes that function in the catabolism of H-, G-, and S-type aromatics, and that there are differences in the role of LigR in N. aromaticivorans and S. lignivorans. A comparative genomic analysis predicted that LigR homologs and the aromatic-metabolizing genes that it directly regulates are often co-localized in the genomes of Sphingomonadales, but often not found in this arrangement in many other known aromatic metabolizing bacteria.

Aromatic Compound Degradation↗
DOE OSTI2020

Direct Observation of the Dynamics of Single-Cell Metabolic Activity during Microbial Diauxic Growth

Understanding how genetic information is realized as the behavior of individual cells is a long-term goal of biology but represents a significant technological challenge. In clonal microbial populations, variation in gene regulation is often interpreted as metabolic heterogeneity. This follows the central dogma of biology, in which information flows from DNA to RNA to protein and ultimately manifests as activity. At present, DNA and RNA can be characterized in single cells, but the abundance and activity of proteins cannot. Inferences about metabolic activity usually therefore rely on the assumption that transcription reflects activity. By tracking the atoms from which they build their biomass, we make direct observations of growth rate and substrate specialization in individual cells throughout a period of growth in a changing environment. This approach allows the flow of information from DNA to be constrained from the distal end of the regulatory cascade and will become an essential tool in the rapidly advancing field of single-cell metabolism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Multi-omic characterization of a soil microbial consortium reveals critical role of succinate and glutamate metabolism during calcium carbonate precipitation

Microbially induced calcium carbonate precipitation (MICP) holds potential for use in soil stabilization and carbon sequestration, with the overall efficiency of the process being a major determinant for use in many environmental and civil engineering applications. While the biogeochemical pathways and enzymes driving MICP are known, the microbial metabolic networks and community dynamics underlying such precipitation remain poorly characterized. To address this gap, we developed a four-member consortium of soil bacteria (Curtobacterium flaccumfaciens, Rhodococcus qingshengii, Microbacterium sp., and Bacillus toyonensis), termed carbon storing consortium - A (CSC-A), that is capable of MICP. Prior work shows that MICP production is higher in CSC-A compared to the sum of carbonate produced by each member, suggesting carbonate production is driven by consortium dynamics. To that end we used a multi-omic integration approach of genomics, transcriptomics, and metabolomics to investigate potential inter-species interactions that may influence the MICP phenotype. Genomic life history characterizations identified evidence of niche specialization by B. toyonensis and Microbacterium, while metatranscriptomic analysis suggests R. qingshengii is a keystone species during growth in urea. By comparing individual species’ metabolomes to the metabolic profile of a shared well of precipitated metabolites, we identified over 200 metabolites predicted to be produced or consumed by CSC-A members. Integrating both data types to search the KEGG reactome highlighted a network centered around glutamine metabolism and branched chain amino acid biosynthesis under regulation during CSC-A growth in urea. Succinate metabolism was also a major node in this network and laboratory assays confirmed that increasing the amount of succinate in the growth medium leads to increased carbonate precipitation by CSC-A, a critical confirmation of our modeling approach. By isolating and identifying the interconnected metabolic components underlying MICP in CSC-A, we identified keystone taxa, metabolites, and pathways important for future optimization of the application of this consortia to carbonate precipitation.

carbon storing consortium - A (CSC-A)↗
DOE OSTI2024

Progression of herpesvirus infection remodels mitochondrial organization and metabolism

Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca 2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A KBase Case Study on Genome-wide Transcriptomics and Plant Primary Metabolism in Sorghum

A better understanding of the genetic and metabolic mechanisms that confer stress resistance and tolerance in plants is key to engineering new crops through advanced breeding technologies. This requires a systems biology approach that builds on a genome-wide understanding of the regulation of gene expression, plant metabolism, physiology and growth. In this study, we examine the response to drought stress in Sorghum, as we leverage the tools for transcriptomics and plant metabolic modeling we have implemented at the U.S. Department of Energy Systems Biology Knowledgebase (KBase). KBase enables researchers worldwide to collaborate and advance research by allowing them to upload private or public data into the KBase Narrative Interface, empowering them to analyze this data using a rich, extensible array of computational and data-analytics tools, and allows them to securely share scientific workflows and conclusions. We demonstrate how to use the current RNA-seq tools in KBase, applicable to both plants and microbes, to assemble and quantify long transcripts and identify differentially expressed genes effectively. More specifically, we demonstrate the utility of the platform by identifying key genes that are differentially expressed during drought-stress in Sorghum bicolor, which is an important sustainable production crop plant. We then show how to use KBase tools to predict the membership of genes in metabolic pathways and examine expression data in the context of metabolic subsystems. We demonstrate the power of the platform by making the data analysis and interpretation available to the biologists in the reproducible, re-usable, point-and-click format of a KBase Narrative thus promoting FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles for scientific data management and stewardship.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Function, Structure, and Regulation of Nitrogen Fixation-like Metalloproteins for Nitrogen, Energy, Carbon, and Sulfur Metabolism

Nitrogenases (N 2 ases) and nitrogen fixation-like (NFL) systems play distinct roles in nitrogen, carbon, sulfur, and energy metabolism based on their fundamental differences in structure and metallocofactor identity. As new NFL systems have recently been identified and characterized, striking parallels and differences compared to N 2 ase structure, catalysis, and regulation have emerged. NFL systems use metallocofactors that span from simple [4Fe-4S] clusters to complex clusters akin to FeMo-co, previously only thought to occur in N 2 ase. This review describes the present state of knowledge on the function, structure, catalytic mechanisms, and regulation of NFL systems that perform distinct biological roles across all three domains of life. Recent advancements in N 2 ase spectroscopic techniques for probing metallocofactor structure and electronic states guide current and future work on how each NFL system catalyzes its specific biological reaction(s). Key knowledge gaps and needed areas of research for uncovering the specific metallocofactors and structural motifs that are at the heart of NFL system reaction specificity, along with how these systems are regulated, are discussed.

Bacteria↗
DOE OSTI2022

Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production

Abstract Branched-chain amino acid (BCAA) metabolism fulfills numerous physiological roles and can be harnessed to produce valuable chemicals. However, the lack of eukaryotic biosensors specific for BCAA-derived products has limited the ability to develop high-throughput screens for strain engineering and metabolic studies. Here, we harness the transcriptional regulator Leu3p from Saccharomyces cerevisiae to develop a genetically encoded biosensor for BCAA metabolism. In one configuration, we use the biosensor to monitor yeast production of isobutanol, an alcohol derived from valine degradation. Small modifications allow us to redeploy Leu3p in another biosensor configuration that monitors production of the leucine-derived alcohol, isopentanol. These biosensor configurations are effective at isolating high-producing strains and identifying enzymes with enhanced activity from screens for branched-chain higher alcohol (BCHA) biosynthesis in mitochondria as well as cytosol. Furthermore, this biosensor has the potential to assist in metabolic studies involving BCAA pathways, and offers a blueprint to develop biosensors for other products derived from BCAA metabolism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Persistent urinary metabolic signatures in children with type 1 diabetes

There are an estimated 3.7 million people with undiagnosed type 1 diabetes (T1D), living primarily in poor areas of the globe. Therefore, there is a need for non-invasive, affordable tests to provide accurate diagnosis despite the time post-disease onset and fasting state. Here, we studied persistent urinary T1D biomarkers that can be used to develop such tests. Here, we analyzed the urine metabolomes of three independent cohorts of samples collected within 48 h (from Indiana University), and 1 year (from University of Colorado) and 1–10 years (6 years in average) (from Children’s National Medical Center) post-diagnosis. Samples were submitted to gas chromatography-mass spectrometry and machine learning an0alyses to determine diagnostic metabolite panels. The data were also mapped into a metabolic pathway to understand persistently regulated processes in T1D. Seven metabolites showed consistent increases in all three cohorts: d-glucose, d-mannose, myo-inositol, 3-hydroxyisobutyric acid, gluconolactone, d-gluconic acid, and d-glucuronic acid. A combination of machine learning analysis and metabolite ratios as biomarker candidates diagnosed T1D with high sensitivity and specificity across different cohorts and times. Mapping the regulated metabolites into a pathway showed impairment in glycolysis and overflow of glucose towards other pathways in subjects with T1D that was persistent over time. We identified and cross-validated highly specific and sensitive urinary biomarkers. This opens opportunities to develop affordable, robust, and non-invasive tests. The results also show that most of the biomarkers were signatures of dysregulated glucose metabolism.

Type 1 diabetes↗
DOE OSTI2021

miR-23b Ameliorates nonalcoholic steatohepatitis by targeting Acyl-CoA thioesterases 4

Non-alcoholic fatty liver disease (NAFLD) and its more advanced stages, Non-alcoholic steatohepatitis and Cirrhosis, are the most common liver diseases in the worldwide, especially in developing countries. NAFLD is distinguished by the accumulation of triglycerides within hepatocytes. An increasing body of evidence suggests that hepatic MicroRNAs play an important role in NAFLD by controlling lipid metabolism, inflammation, and fibrosis. However, the precise causative functions of miRNA in NAFLD remain unknown. Here, we discovered that mice lacking MicroRNA-23b developed NAFLD-like phenotypes such as increased serum triglyceride and lipid droplet accumulation. In db/db mice fed a high fat diet, MicroRNA-23b overexpression reduced liver weight and alleviated liver inflammation, apoptosis, and fibrosis. MicroRNA-23b regulates the acyl-CoA metabolic process via Acyl-CoA thioesterase 4 (Acot4), which interacts with Acetyl CoA Carboxylase (ACC), according to the RNA-seq analysis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Omics-driven onboarding of the carotenoid producing red yeast Xanthophyllomyces dendrorhous CBS 6938

Transcriptomics is a powerful approach for functional genomics and systems biology, yet it can also be used for genetic part discovery. Here, we derive constitutive and light-regulated promoters directly from transcriptomics data of the basidiomycete red yeast Xanthophyllomyces dendrorhous CBS 6938 (anamorph Phaffia rhodozyma) and use these promoters with other genetic elements to create a modular synthetic biology parts collection for this organism. X. dendrorhous is currently the sole biotechnologically relevant yeast in the Tremellomycete class-it produces large amounts of astaxanthin, especially under oxidative stress and exposure to light. Thus, we performed transcriptomics on X. dendrorhous under different wavelengths of light (red, green, blue, and ultraviolet) and oxidative stress. Differential gene expression analysis (DGE) revealed that terpenoid biosynthesis was primarily upregulated by light through crtI, while oxidative stress upregulated several genes in the pathway. Further gene ontology (GO) analysis revealed a complex survival response to ultraviolet (UV) where X. dendrorhous upregulates aromatic amino acid and tetraterpenoid biosynthesis and downregulates central carbon metabolism and respiration. The DGE data was also used to identify 26 constitutive and regulated genes, and then, putative promoters for each of the 26 genes were derived from the genome. Simultaneously, a modular cloning system for X. dendrorhous was developed, including integration sites, terminators, selection markers, and reporters. Each of the 26 putative promoters were integrated into the genome and characterized by luciferase assay in the dark and under UV light. The putative constitutive promoters were constitutive in the synthetic genetic context, but so were many of the putative regulated promoters. Notably, one putative promoter, derived from a hypothetical gene, showed ninefold activation upon UV exposure. Thus, this study reveals metabolic pathway regulation and develops a genetic parts collection for X. dendrorhous from transcriptomic data. Therefore, this study demonstrates that combining systems biology and synthetic biology into an omics-to-parts workflow can simultaneously provide useful biological insight and genetic tools for nonconventional microbes, particularly those without a related model organism. This approach can enhance current efforts to engineer diverse microbes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Volatile traits expand the microbial playbook

Microbial metabolic functions are increasingly conceptualized as fitness-regulating traits. However, volatile compounds (the volatilome), despite their key roles in metabolism and ecology, are often overlooked in trait-based frameworks. We propose that volatile traits not only reflect ecological strategies but also shape them by mediating responses to selection pressures. Their volatility affects diffusion, substrate access, and interactions across space, conferring selective advantages as resources or waste products. We outline approaches to incorporate volatile traits into predictive models to improve understanding of microbial selection and community dynamics. Furthermore, this integration enables a more holistic view of microbial life by accounting for the ecological and evolutionary consequences of volatile-mediated processes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth

Summary The first step in chloroplast de novo fatty acid synthesis is catalysed by acetyl‐CoA carboxylase (ACCase). As the rate‐limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homologue of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein interacts with the Chlamydomonas α‐carboxyltransferase (Crα‐CT) subunit of the ACCase by yeast two‐hybrid protein–protein interaction assay. Three independent CRISPR‐Cas9 mediated knockout mutants for CrCTI1 each produced an ‘enhanced oil’ phenotype, accumulating 25% more total fatty acids and storing up to fivefold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of the crcti1 mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mapped in vivo phosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα‐CT. However, mutating all six predicted phosphorylation sites within Crα‐CT to create a phosphomimetic mutant reduced this pairwise interaction significantly. Comparative proteomic analyses of the crcti1 mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β‐oxidation pathways, to enable cells to adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for the genetic engineering of microalgae for biotechnology purposes.

Li, Zhongze [Aix‐Marseille Université, CEA, CNRS, ↗
DOE OSTI2024

Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training

Abstract This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90‐min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O 2 peak) exercise using indirect calorimetry, and 6‐6‐[ 2 H 2 ]‐glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE ( p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased ( p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST ( p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole‐body and skeletal muscle fat metabolism.

Drummer, Devin J.↗
DOE OSTI2021

CreA-mediated repression of gene expression occurs at low monosaccharide levels during fungal plant biomass conversion in a time and substrate dependent manner

Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural basis of agonist specificity of α 1A -adrenergic receptor

α 1 -adrenergic receptors (α 1 -ARs) play critical roles in the cardiovascular and nervous systems where they regulate blood pressure, cognition, and metabolism. However, the lack of specific agonists for all α 1 subtypes has limited our understanding of the physiological roles of different α 1 -AR subtypes, and led to the stagnancy in agonist-based drug development for these receptors. Here we report cryo-EM structures of α 1A -AR in complex with heterotrimeric G-proteins and either the endogenous common agonist epinephrine or the α 1A -AR-specific synthetic agonist A61603. These structures provide molecular insights into the mechanisms underlying the discrimination between α 1A -AR and α 1B -AR by A61603. Guided by the structures and corresponding molecular dynamics simulations, we engineer α 1A -AR mutants that are not responsive to A61603, and α 1B -AR mutants that can be potently activated by A61603. Together, these findings advance our understanding of the agonist specificity for α 1 -ARs at the molecular level, opening the possibility of rational design of subtype-specific agonists.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Salinity tolerance mechanisms of an Arctic Pelagophyte using comparative transcriptomic and gene expression analysis

Abstract Little is known at the transcriptional level about microbial eukaryotic adaptations to short-term salinity change. Arctic microalgae are exposed to low salinity due to sea-ice melt and higher salinity with brine channel formation during freeze-up. Here, we investigate the transcriptional response of an ice-associated microalgae over salinities from 45 to 8. Our results show a bracketed response of differential gene expression when the cultures were exposed to progressively decreasing salinity. Key genes associated with salinity changes were involved in specific metabolic pathways, transcription factors and regulators, protein kinases, carbohydrate active enzymes, and inorganic ion transporters. The pelagophyte seemed to use a strategy involving overexpression of Na + -H + antiporters and Na + -Pi symporters as salinity decreases, but the K + channel complex at higher salinities. Specific adaptation to cold saline arctic conditions was seen with differential expression of several antifreeze proteins, an ice-binding protein and an acyl-esterase involved in cold adaptation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells

The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a nonmeiotic program of chromosome loss. The genetic diversity afforded by parasex impacts clinically relevant features including drug resistance and virulence, and yet the factors influencing genome instability in C. albicans are not well defined. To understand how environmental cues impact genome instability, we monitored ploidy change following tetraploid cell growth in a panel of different carbon sources. We found that growth in one carbon source, D-tagatose, led to high levels of genomic instability and chromosome loss in tetraploid cells. This sugar is a stereoisomer of L-sorbose which was previously shown to promote karyotypic changes in C. albicans. However, while expression of the SOU1 gene enabled utilization of L-sorbose, overexpression of this gene did not promote growth in D-tagatose, indicating differences in assimilation of the two sugars. In addition, genome sequencing of multiple progenies recovered from D-tagatose cultures revealed increased relative copy numbers of chromosome 4, suggestive of chromosome-level regulation of D-tagatose metabolism. Together, these studies identify a novel environmental cue that induces genome instability in C. albicans, and further implicate chromosomal changes in supporting metabolic adaptation in this species.

59 BASIC BIOLOGICAL SCIENCES↗