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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 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

iNovo479: Metabolic Modeling Provides a Roadmap to Optimize Bioproduct Yield from Deconstructed Lignin Aromatics by Novosphingobium aromaticivorans

Lignin is an abundant renewable source of aromatics and precursors for the production of other organic chemicals. However, lignin is a heterogeneous polymer, so the mixture of aromatics released during its depolymerization can make its conversion to chemicals challenging. Microbes are a potential solution to this challenge, as some can catabolize multiple aromatic substrates into one product. Novosphingobium aromaticivorans has this ability, and its use as a bacterial chassis for lignin valorization could be improved by the ability to predict product yields based on thermodynamic and metabolic inputs. In this work, we built a genome-scale metabolic model of N. aromaticivorans, iNovo479, to guide the engineering of strains for aromatic conversion into products. iNovo479 predicted product yields from single or multiple aromatics, and the impact of combinations of aromatic and non-aromatic substrates on product yields. We show that enzyme reactions from other organisms can be added to iNovo479 to predict the feasibility and profitability of producing additional products by engineered strains. Thus, we conclude that iNovo479 can help guide the design of bacteria to convert lignin aromatics into valuable chemicals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro

Persistence is a bet-hedging strategy in bacterial populations that increases antibiotic tolerance and leads to the establishment of latent infections. In this study, we demonstrated that a synthetic non-toxic taxane-based reversal agent (tRA), developed as an inhibitor of ABC transporter systems in mammalian cancer cells, enhanced antibiotic killing of persister populations from different pathogens, including Burkholderia, Pseudomonas, Francisella, and Yersinia. Acting as an inhibitor of bacterial efflux at 100 nM, tRA99020 enhanced antibiotic efficiency and suppressed the production of natural products of Burkholderia species polyketide synthase (PKS) function. We demonstrate that the metabolites produced by PKS in response to stress by different antibiotics act as inhibitors of mammalian histone deacetylase activity and stimulate cell death. Applying a single-molecule fluorescence in situ hybridization (smFISH) assay, we analyzed on a single-cell level the activation profiles of the persistence regulating pks gene in Burkholderia thailandensis treated with tRA99020 and antibiotics. We posit that a multi-pronged approach encompassing antibiotic therapies and inhibition of efflux systems and fatty acid catabolism will be required for efficient eradication of persistent bacterial populations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Specific Bacterial Taxa and Their Metabolite, DHPS, May Be Linked to Gut Dyshomeostasis in Patients with Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Background: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs—amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD)—and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases.

Nutrition & Dietetics↗
DOE OSTI2022

Light-Dependence of Formate (C1) and Acetate (C2) Transport and Oxidation in Poplar Trees

Although apparent light inhibition of leaf day respiration is a widespread reported phenomenon, the mechanisms involved, including utilization of alternate respiratory pathways and substrates and light inhibition of TCA cycle enzymes are under active investigation. Recently, acetate fermentation was highlighted as a key drought survival strategy mediated through protein acetylation and jasmonate signaling. Here, we evaluate the light-dependence of acetate transport and assimilation in Populus trichocarpa trees using the dynamic xylem solution injection (DXSI) method developed here for continuous studies of C1 and C2 organic acid transport and light-dependent metabolism. Over 7 days, 1.0 L of [13C]formate and [13C2]acetate solutions were delivered to the stem base of 2-year old potted poplar trees, while continuous diurnal observations were made in the canopy of CO2, H2O, and isoprene gas exchange together with δ13CO2. Stem base injection of 10 mM [13C2]acetate induced an overall pattern of canopy branch headspace 13CO2 enrichment (δ13CO2 +27‰) with a diurnal structure in δ13CO2 reaching a mid-day minimum followed by a maximum shortly after darkening where δ13CO2 values rapidly increased up to +12‰. In contrast, 50 mM injections of [13C]formate were required to reach similar δ13CO2 enrichment levels in the canopy with δ13CO2 following diurnal patterns of transpiration. Illuminated leaves of detached poplar branches pretreated with 10 mM [13C2]acetate showed lower δ13CO2 (+20‰) compared to leaves treated with 10 mM [13C]formate (+320‰), the opposite pattern observed at the whole plant scale. Following dark/light cycles at the leaf-scale, rapid, strong, and reversible enhancements in headspace δ13CO2 by up to +60‰ were observed in [13C2]acetate-treated leaves which showed enhanced dihydrojasmonic acid and TCA cycle intermediate concentrations. The results are consistent with acetate in the transpiration stream as an effective activator of the jasmonate signaling pathway and respiratory substrate. The shorter lifetime of formate relative to acetate in the transpiration stream suggests rapid formate oxidation to CO2 during transport to the canopy. In contrast, acetate is efficiently transported to the canopy where an increased allocation towards mitochondrial dark respiration occurs at night. The results highlight the potential for an effective integration of acetate into glyoxylate and TCA cycles and the light-inhibition of citrate synthase as a potential regulatory mechanism controlling the diurnal allocation of acetate between anabolic and catabolic processes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Signatures of transposon-mediated genome inflation, host specialization, and photoentrainment in Entomophthora muscae and allied entomophthoralean fungi

Despite over a century of observations, the obligate insect parasites within the order Entomophthorales remain poorly characterized at the genetic level. In this manuscript, we present a genome for a laboratory-tractable Entomophthora muscae isolate that infects fruit flies. Our E. muscae assembly is 1.03 Gb, consists of 7810 contigs and contains 81.3% complete fungal BUSCOs. Using a comparative approach with recent datasets from entomophthoralean fungi, we show that giant genomes are the norm within Entomophthoraceae owing to extensive, but not recent, Ty3 retrotransposon activity. In addition, we find that E. muscae and its closest allies possess genes that are likely homologs to the blue-light sensor white-collar 1, a Neurospora crassa gene that has a well-established role in maintaining circadian rhythms. We uncover evidence that E. muscae diverged from other entomophthoralean fungi by expansion of existing families, rather than loss of particular domains, and possesses a potentially unique suite of secreted catabolic enzymes, consistent with E. muscae’s species-specific, biotrophic lifestyle. Finally, we offer a head-to-head comparison of morphological and molecular data for species within the E. muscae species complex that support the need for taxonomic revision within this group. Altogether, we provide a genetic and molecular foundation that we hope will provide a platform for the continued study of the unique biology of entomophthoralean fungi.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Methyl jasmonate effects on sugarbeet root responses to postharvest dehydration

Background: Sugarbeet (Beta vulgaris L.) roots are stored under conditions that cause roots to dehydrate, which increases postharvest losses. Although exogenous jasmonate applications can reduce drought stress in intact plants, their ability to alleviate the effects of dehydration in postharvest sugarbeet roots or other stored plant products is unknown. Research was conducted to determine whether jasmonate treatment could mitigate physiological responses to dehydration in postharvest sugarbeet roots. Methods: Freshly harvested sugarbeet roots were treated with 10 µM methyl jasmonate (MeJA) or water and stored under dehydrating and non-dehydrating storage conditions. Changes in fresh weight, respiration rate, wound healing, leaf regrowth, and proline metabolism of treated roots were investigated throughout eight weeks in storage. Results: Dehydrating storage conditions increased root weight loss, respiration rate, and proline accumulation and prevented leaf regrowth from the root crown. Under dehydrating conditions, MeJA treatment reduced root respiration rate, but only in severely dehydrated roots. MeJA treatment also hastened wound-healing, but only in the late stages of barrier formation. MeJA treatment did not impact root weight loss or proline accumulation under dehydrating conditions or leaf regrowth under non-dehydrating conditions. Both dehydration and MeJA treatment affected expression of genes involved in proline metabolism. In dehydrated roots, proline dehydrogenase expression declined 340-fold, suggesting that dehydration-induced proline accumulation was governed by reducing proline degradation. MeJA treatment altered proline biosynthetic and catabolic gene expression, with greatest effect in nondehydrated roots. Overall, MeJA treatment alleviated physiological manifestations of dehydration stress in stored roots, although the beneficial effects were small. Postharvest jasmonate applications, therefore, are unlikely to significantly reduce dehydrationrelated storage losses in sugarbeet roots.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Study of the effect of the trancription factor SARO_RS14285 in aromatics degradation in Novosphingobium aromaticivorans

Novosphingobium aromaticivorans DSM12444 is a bacterium capable of catabolizing several lignin aromatics. A main degradation pathway for these compounds is the protocatechuate (PCA) meta-cleavage. Nevertheless, the transcriptional regulation of this pathway is still unknown. Immediately upstream of the genes encoding the enzymes for this pathway, the LysR-type transcription factor (LTTF) SARO_RS14285 was identified. To evaluate the functionality of this LTTF, a deletion mutant was constructed. A transcriptomic analysis of the mutant strain cultured in several aromatic compounds is included in this report. Overall design: RNA-seq profiling of the WT and the deletion mutant cultured in minimal medium with glucose and one of the following aromatics: protocatechuic acid (PCA), 4-coumaric acid (4-CA), vanillic acid (VA) or syringic acid (SA).

aromatics↗
NASA NTRS1972

Threonine deaminase from extremely halophilic bacteria - Cooperative substrate kinetics and salt dependence.

The effect of salt on the activity, stability, and allosteric properties of catabolic threonine deaminase from Halobacterium cutirubrum was studied. The enzyme exhibits sigmoidal kinetics with the substrate, threonine. The Hill slope is 1.55 at pH 10. The enzyme is activated by ADP at low substrate concentrations. In the presence of this effector, sigmoidal kinetics are no longer observed. At pH 10, in the absence of ADP, enzyme activity increases with increasing NaCl concentration from 0 to 4 M.

Lieberman, M. M.↗
NASA NTRS1973

Nonthermal metabolic response of rats to He-O2, N2-O2, and Ar-O2 at 1 atm.

Experiments were performed to describe qualitatively and quantitatively the nonthermal metabolic response of rats to normoxic mixtures of helium, nitrogen, or argon at 1 atm ambient pressure. Hypoxic mixtures were similarly tested to determine any differences in hypoxic response as a function of the diluent gas. Rats exposed to argon for 5 days had a reduced metabolic rate relative to nitrogen, as evidenced by oxygen and food consumption, CO2 production, and the catabolism of radiosubstrates. While some parameters indicated that helium increased metabolic rate, oxygen consumption did not significantly differ from that in nitrogen. The physiologic and metabolic response to an imposed hypoxia varied among the different environments. Certain indices suggested that the hypoxic effects were less severe in helium and more pronounced in argon than in nitrogen. The mechanisms by which the diluent gases produced the observed changes could not be identified, but some possibilities are discussed.

Schatte, C. L.↗
NASA NTRS1973

Investigation of the effect of stress on the chemistry, metabolism, and biophysics of collagen

The research is reported concerning the effect of stress on the chemistry in the connective tissue of the rat. It was found that within a day after administration of cortisol (stress harmone), a significant amount of the insoluble collagen disappeared from the skin. It is concluded that the abrupt catabolism of cutaneous collagen releases peptides. These peptides are rapidly degraded to free amino acids which are active in effecting liver glycogen synthesis, and provide a major energy source to assist the animal in the fight or flight reaction. It is proposed that cutaneous collagen represents a reserve energy pool, which can be mobilized via stress harmones.

Houck, J. C.↗
NASA NTRS1977

Potential use of nutritional factors to optimize performance under stress

A study of the effects of amino acids on hypothalamo-pituitary capacity to secrete ACTH, and the response of the adrenal gland in terms of corticosterone level in the plasma was discussed in the first part of this report. Second, the report includes a study of the response of protein metabolism in various levels of corticosterone elevation in the plasma. This second part is regarded as having considerable significance for space travel, since this data indicate a threshold level of plasma corticosteroids above which there is increased catabolism of muscle protein.

Munro, H. N.↗
NASA NTRS1980

Metabolism during hypodynamia

Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

Federov, I. V.↗
NASA NTRS1982

Evaluation of the response of rat skeletal muscle to a model of weightlessness

Suspension of rats in a head-down tilt position such that their hind limbs are non-load bearing has been proposed as a model for weightlessness. Changes observed in metabolism, bone formation (Morey et al., 1979), and muscle catabolism (Mussachia et al., 1980) support the validity of the model. To further document this model, the effects of suspension on the mechanical, biochemical and histochemical characteristics of two hind limb skeletal muscles, the gastrocnemius and the soleus, are investigated.

Templeton, G. H.↗
NASA NTRS1983

The validity of an animal model for experiments related to weightlessness

Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.

Musacchia, X. J.↗
NASA NTRS1985

Chemolithotrophy and physiology of bacterial nutrient limitation

An overview of the physiology of chemolithotrophic bacteria, particularly the thiobacilli, was presented. In these bacteria unique physiological traits are expressed during nutrient limited growth. Different physiological types of chemolithotrophs, pathways of sulfur oxidation, and electron transport in the thiobacilli, problems encountered by chemolithotrophs in the generation of reducing power, and some explanations of the phenomenon of obligate chemolithotrophy were considered. Mixotrophy in the thiobacilli has been studied extensively both under nutrient excess and limitation. In nature, bacteria usually grow under nutrient limitation. Yet the bulk of our knowledge of microbial metabolic function is derived from bacteria grown in laboratory batch cultures containing a great abundance of nutrients. Microbial behavior in these two types of environments can be very different, indicating the need for basing an understanding of microbial ecology on studies that rely on cultivation of microorganisms under nutrient limitation. Nutrient limited bacteria differ in several ways from those growing in large quantities of nutrients. They have different surface structures and make a much fuller use of their metabolic potential, especially by the synthesis of unique pathways of catabolic enzymes.

Matin, A.↗