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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

The Roles of Nicotinamide Adenine Dinucleotide Phosphate Reoxidation and Ammonium Assimilation in the Secretion of Amino Acids as Byproducts of Clostridium thermocellum

Improving the ethanol yield of C. thermocellum is important for the industrial implementation of this microorganism in consolidated bioprocessing. A central role of NADPH in driving amino acid byproduct formation was demonstrated by eliminating the NADPH-supplying malate shunt and separately by changing the cofactor specificity in ammonium assimilation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Leafweb: Leaf Gas Exchange and Pulse-Amplitude Modulated Fluorometry for C4 Species, June 2026 Release

This dataset contains leaf gas exchange and Pulse-Amplitude Modulated (PAM) fluorometry for 98 C4 species. The C4 photosynthetic pathway employs specialized CO2 concentration mechanisms and Kranz anatomy to enrich CO2 concentration around Rubisco, the enzyme that catalyzes carbon fixation in the Calvin-Benson cycle to suppress photorespiration and increase the use efficiencies of light, nitrogen, and water as compared to the C3 photosynthetic pathways. Large-scale C4 photosynthetic datasets are relatively scarce, which has affected C4 photosynthesis research. To improve C4 photosynthetic data availability, Leafweb organized an effort to systematically collect, compile, standardize, and organize measurements of leaf gas exchange and/or Pulse-Amplitude Modulated (PAM) fluorometry of C4 species. This derived a C4 photosynthetic dataset containing measurements made by independent researchers in multiple countries in various environments (field, garden, or greenhouse). It covers three biochemical subtypes – the nicotinamide adenine dinucleotide phosphate-malic enzyme (NADP-ME), nicotinamide adenine dinucleotide-malic enzyme (NAD-ME), and phosphoenolpyruvate carboxykinase (PEP-CK) subtypes. This dataset is useful for using Artificial Intelligence / Machine Learning and mechanistic models to study C4 photosynthesis and compare across different biochemical subtypes. This dataset contains 3 compressed (*.zip) folders containing 1,892 data files in comma-separate values (*.csv) format. Additional metadata are provided: one data dictionary and a file-level metadata file in comma-separate values (*.csv) format and a user guide in PDF (*.pdf) format.

Zhou, Haoran [Tianjin University, China]↗
DOE OSTI2021

Nucleobase-Functionalized Poly(alkylthiophene)s: One-Pot, Sequential Direct Arylation Polymerization and Deprotection, and Surface Modification for Oil–Water Separations

Direct arylation polymerization (DArP) has emerged as an environmentally friendly, atom efficient method of synthesizing a variety of conjugated polymers. In this work, we report a one-pot approach consisting of DArP followed by Boc deprotection to synthesize a functional, surface-active adenine-containing poly(alkylthiophene). Careful control over the polymerization temperature enables the one-pot polymerization and deprotection strategy for synthesis, with quantitative (>99%) Boc deprotection achieved in 24 h. This temperature-controlled synthesis method reduces extra purification and isolation steps, which makes the total synthesis more efficient and practical, and allows higher molecular weight polymer to be made. We quantify the hydrogen bonding ability of the resulting adenine-containing polythiophene, T Ad -tT 4h , by 1 H NMR host–guest titration studies and analyze the results with the Benesi–Hildebrand model, yielding an association constant of 18.7 M –1 between alkylated thymine and T Ad -tT 4h . We demonstrate that T Ad -tT 4h robustly modifies the surface of cellulosic filter paper (CFP), and the modified cellulosic filter paper, CFP-T Ad -tT 4h , is an effective oil–water separatory filter with superhydrophobic properties (water contact angle (CA) ~151°). The utility of hydrogen bonding interactions between adenine and cellulose highlights the importance of side-chain engineering for creating functional materials.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Immobilization of Cyanines in DNA Produces Systematic Increases in Fluorescence Intensity

Cyanines are useful fluorophores for a myriad of biological labeling applications, but their interactions with biomolecules are unpredictable. Cyanine fluorescence intensity can be highly variable due to complex photoisomerization kinetics, which are exceedingly sensitive to the surrounding environment. This introduces large errors in Förster resonance energy transfer (FRET)-based experiments where fluorescence intensity is the output parameter. However, this environmental sensitivity is a strength from a biological sensing point of view if specific relationships between biomolecular structure and cyanine photophysics can be identified. We describe a set of DNA structures that modulate cyanine fluorescence intensity through the insertion of adenine or thymine bases. These structures simultaneously provide photophysical predictability and tunability. We characterize these structures using steady-state fluorescence measurements, fluorescence correlation spectroscopy (FCS), and time-resolved photoluminescence (TRPL). Here, we find that the photoisomerization rate decreases over an order of magnitude across the adenine series, which is consistent with increasing immobilization of the cyanine moiety by the surrounding DNA structure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Mechanisms in the Synthesis of S -Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study

The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η 1 -keto-S-η 2 -5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J. Organometal. Chem. 2021, 943, 121810). Presently, we studied canonical and alternative mechanisms compared to models of the entire enzyme structure. We disproved the η 2 -Zn(II) complex, and discovered a canonical hydride transfer from biomimetic 1,4-NADH, 1, to the Zn(II) bound prochiral ketone substrate, followed by a new proton relay, consisting of a water chain connecting His51 to Ser48 that accomplished the S-alkoxy anion's protonation to yield the final S-alcohol product. The HLADH catalysis, with biomimetic co-factor, 1, that replaced the ribose group, the 5'-diphosphate groups, and the adenine nucleotide with a N-benzyl group, has provided a new paradigm for the design of other structures of 1,4-NADH biomimetic co-factors, including their economic value in biocatalysis reactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Surface Reorganization of Transition Metal Dichalcogenide Nanoflowers for Efficient Electrochemical Coenzyme Regeneration

In the past 20 years, enzymatic conversions have been intensely examined as a practical and environmentally friendly alternative to traditional organocatalytic conversions for chemicals and pharmaceutical intermediate production. Out of all commercial enzymes, more than one-fourth are oxidoreductases that operate in tandem with coenzymes, typically nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH). Enzymes utilize coenzymes as a source for electrons, protons, or holes. Unfortunately, coenzymes can be exorbitant; thus, recycling coenzymes is paramount to establishing a sustainable and affordable cell-free enzymatic catalyst system. Herein, cost-effective transition metal dichalcogenides (TMDCs), 2H-MoS 2 , 2H-WS 2 , and 2H-WSe 2 , were employed for the first time for direct electrochemical reduction of NAD + to the active form of the NADH (1,4-NADH). Of the three TMDCs, 2H-WSe 2 shows optimal activity, producing 1,4 NADH at a rate of 6.5 μmol cm –2 h –1 and a faradaic efficiency of 45% at -0.8 V vs Ag/AgCl. Interestingly, a self-induced surface reorganization process was identified, where the native surface oxide grown in the air was spontaneously removed in the electrochemical process, resulting in the activation of TMDCs.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Electrochemical cofactor recycling of bacterial microcompartments

Bacterial microcompartments (BMCs) are prokaryotic organelles that consist of a protein shell which sequesters metabolic reactions in its interior. While most of the substrates and products are relatively small and can permeate the shell, many of the encapsulated enzymes require cofactors that must be regenerated inside. We have analyzed the occurrence of an enzyme previously assigned as a cobalamin (vitamin B 12 ) reductase and, curiously, found it in many unrelated BMC types that do not employ B 12 cofactors. We propose Nicotinamide adenine dinucleotide (NAD+) regeneration as the function of this enzyme and name it Metabolosome Nicotinamide Adenine Dinucleotide Hydrogen (NADH) dehydrogenase (MNdh). Its partner shell protein BMC-T SE (tandem domain BMC shell protein of the single layer type for electron transfer) assists in passing the generated electrons to the outside. We support this hypothesis with bioinformatic analysis, functional assays, Electron Paramagnetic Resonance spectroscopy, protein voltammetry, and structural modeling verified with X-ray footprinting. This finding represents a paradigm for the BMC field, identifying a new, widely occurring route for cofactor recycling and a new function for the shell as separating redox environments.

bacterial microcompartment↗
DOE OSTI2020

Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs

We recently reported the presence of nicotinamide adenine dinucleotide (NAD)-capped RNAs in mammalian cells and a role for DXO and the Nudix hydrolase Nudt12 in decapping NAD-capped RNAs (deNADding) in cells. Analysis of 5'caps has revealed that in addition to NAD, mammalian RNAs also contain other metabolite caps including flavin adenine dinucleotide (FAD) and dephosphoCoA (dpCoA). In the present study we systematically screened all mammalian Nudix proteins for their potential deNADing, FAD cap decapping (deFADding) and dpCoA cap decapping (deCoAping) activity. We demonstrate that Nudt16 is a novel deNADding enzyme in mammalian cells. Additionally, we identified seven Nudix proteins—Nudt2, Nudt7, Nudt8, Nudt12, Nudt15, Nudt16 and Nudt19, to possess deCoAping activity in vitro. Moreover, our screening revealed that both mammalian Nudt2 and Nudt16 hydrolyze FAD-capped RNAs in vitro with Nudt16 regulating levels of FAD-capped RNAs in cells. All decapping activities identified hydrolyze the metabolite cap substrate within the diphosphate linkage. Crystal structure of human Nudt16 in complex with FAD at 2.7 Å resolution provide molecular insights into the binding and metal-coordinated hydrolysis of FAD by Nudt16. In summary, our study identifies novel cellular deNADding and deFADding enzymes and establishes a foundation for the selective functionality of the Nudix decapping enzymes on non-canonical metabolite caps.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural snapshots of base excision by the cancer-associated variant MutY N146S reveal a retaining mechanism

Abstract DNA glycosylase MutY plays a critical role in suppression of mutations resulted from oxidative damage, as highlighted by cancer-association of the human enzyme. MutY requires a highly conserved catalytic Asp residue for excision of adenines misinserted opposite 8-oxo-7,8-dihydroguanine (OG). A nearby Asn residue hydrogen bonds to the catalytic Asp in structures of MutY and its mutation to Ser is an inherited variant in human MUTYH associated with colorectal cancer. We captured structural snapshots of N146S Geobacillus stearothermophilus MutY bound to DNA containing a substrate, a transition state analog and enzyme-catalyzed abasic site products to provide insight into the base excision mechanism of MutY and the role of Asn. Surprisingly, despite the ability of N146S to excise adenine and purine (P) in vitro, albeit at slow rates, N146S-OG:P complex showed a calcium coordinated to the purine base altering its conformation to inhibit hydrolysis. We obtained crystal structures of N146S Gs MutY bound to its abasic site product by removing the calcium from crystals of N146S-OG:P complex to initiate catalysis in crystallo or by crystallization in the absence of calcium. The product structures of N146S feature enzyme-generated β-anomer abasic sites that support a retaining mechanism for MutY-catalyzed base excision.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA-binding region

Photolyases (PLs) reverse UV-induced DNA damage using blue light as an energy source. Of these PLs, (6-4) PLs repair (6-4)-lesioned photoproducts. We recently identified a gene from Vibrio cholerae (Vc) encoding a (6-4) PL, but structural characterization is needed to elucidate specific interactions with the chromophore cofactors. Here, we determined the crystal structure of Vc (6-4) PL at 2.5 Å resolution. Our high-resolution structure revealed that the two well-known cofactors, flavin adenine dinucleotide and the photoantenna 6,7-dimethyl 8-ribityl-lumazin (DMRL), stably interact with an α-helical and an α/β domain, respectively. Additionally, the structure has a third cofactor with distinct electron clouds corresponding to a [4Fe-4S] cluster. Moreover, we identified that Asp106 makes a hydrogen bond with water and DMRL, which indicates further stabilization of the photoantenna DMRL within Vc (6-4) PL. Further analysis of the Vc (6-4) PL structure revealed a possible region responsible for DNA binding. The region located between residues 478 to 484 may bind the lesioned DNA, with Arg483 potentially forming a salt bridge with DNA to stabilize further the interaction of Vc (6-4) PL with its substrate. Our comparative analysis revealed that the DNA lesion could not bind to the Vc (6-4) PL in a similar fashion to the Drosophila melanogaster (Dm, (6-4)) PL without a significant conformational change of the protein. The 23rd helix of the bacterial (6-4) PLs seems to have remarkable plasticity, and conformational changes facilitate DNA binding. In conclusion, our structure provides further insight into DNA repair by a (6-4) PL containing three cofactors.

(6-4) lesioned photoproduct↗
DOE OSTI2021

Structure and mechanism of Staphylococcus aureus oleate hydratase (OhyA)

Flavin adenine dinucleotide (FAD)-dependent bacterial oleate hydratases (OhyAs) catalyze the addition of water to isolated fatty acid carbon–carbon double bonds. Staphylococcus aureus uses OhyA to counteract the host innate immune response by inactivating antimicrobial unsaturated fatty acids. Mechanistic information explaining how OhyAs catalyze regiospecific and stereospecific hydration is required to understand their biological functions and the potential for engineering new products. In this study, we deduced the catalytic mechanism of OhyA from multiple structures of S. aureus OhyA in binary and ternary complexes with combinations of ligands along with biochemical analyses of relevant mutants. The substrate-free state shows Arg81 is the gatekeeper that controls fatty acid entrance to the active site. FAD binding engages the catalytic loop to simultaneously rotate Glu82 into its active conformation and Arg81 out of the hydrophobic substrate tunnel, allowing the fatty acid to rotate into the active site. FAD binding also dehydrates the active site, leaving a single water molecule connected to Glu82. This active site water is a hydronium ion based on the analysis of its hydrogen bond network in the OhyA•PEG400•FAD complex. We conclude that OhyA accelerates acid-catalyzed alkene hydration by positioning the fatty acid double bond to attack the active site hydronium ion, followed by the addition of water to the transient carbocation intermediate. Structural transitions within S. aureus OhyA channel oleate to the active site, curl oleate around the substrate water, and stabilize the hydroxylated product to inactivate antimicrobial fatty acids.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Cellular mRNA triggers structural transformation of Ebola virus matrix protein VP40 to its essential regulatory form

The Ebola virus matrix protein VP40 forms distinct structures linked to distinct functions in the virus life cycle. Dimeric VP40 is a structural protein associated with virus assembly, while octameric, ring-shaped VP40 is associated with transcriptional control. In this study, we show that suitable nucleic acid is sufficient to trigger a dynamic transformation of VP40 dimer into the octameric ring. Deep sequencing reveals a binding preference of the VP40 ring for the 3' untranslated region of cellular mRNA and a guanine- and adenine-rich binding motif. Complementary analyses of the nucleic-acid-induced VP40 ring by native mass spectrometry, electron microscopy, and X-ray crystal structures at 1.8 and 1.4 Å resolution reveal the stoichiometry of RNA binding, as well as an interface involving a key guanine nucleotide. The host factor-induced structural transformation of protein structure in response to specific RNA triggers in the Ebola virus life cycle presents unique opportunities for therapeutic inhibition.

3′ UTR↗