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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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All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member of the (multi)gene families present and the metabolic networks that are operative. Additionally, one key to identifying physiological functions for many of these (and other) unknown genes, and their corresponding metabolic networks, awaits the development of technologies to comprehensively study molecular processes at the single cell level in particular tissues and organs, in order to establish the actual metabolic context.

NASA Program Fundamental Space Biology↗
NASA NTRS2003

A quantitative study of oxygen as a metabolic regulator

An acute reduction in oxygen delivery to a tissue is associated with metabolic changes aimed at maintaining ATP homeostasis. However, given the complexity of the human bioenergetic system, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). In particular, we are interested in determining mechanisms relating cellular oxygen concentration to observed metabolic responses at the cellular, tissue, organ, and whole body levels and in quantifying how changes in tissue oxygen availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics, to provide a physicochemical framework that permits quantitative understanding of oxygen as a metabolic regulator. Specifically, the enhancement--sensitivity analysis--permits studying the effects of variations in tissue oxygenation and parameters controlling cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The analysis can distinguish between parameters that must be determined accurately and those that require less precision, based on their effects on model predictions. This capability may prove to be important in optimizing experimental design, thus reducing use of animals.

Non-programmatic↗
NASA NTRS1996

Nitrogen metabolism in Lignifying Pinus taeda cell cultures

The primary metabolic fate of phyenylalanine, following its deamination in plants, is conscription of its carbon skeleton for lignin, suberin, flavonoid, and related metabolite formation. Since this accounts for approximately 30-40% of all organic carbon, an effective means of recycling the liberated ammonium ion must be operative. In order to establish how this occurs, the uptake and metabolism of various 15N-labeled precursors (15N-Phe, 15NH4Cl, 15N-Gln, and 15N-Glu) in lignifying Pinus taeda cell cultures was investigated, using a combination of high performance liquid chromatography, 15N NMR, and gas chromatograph-mass spectrometry analyses. It was found that the ammonium ion released during active phenylpropanoid metabolism was not made available for general amino acid/protein synthesis. Rather it was rapidly recycled back to regenerate phenylalanine, thereby providing an effective means of maintaining active phenylpropanoid metabolism with no additional nitrogen requirement. These results strongly suggest that, in lignifying cells, ammonium ion reassimilation is tightly compartmentalized.

NASA Discipline Number 40-50↗
NASA NTRS2005

Metabolic Reactions among Organic Sulfur Compounds

Sulfur is central to the metabolisms of many organisms that inhabit extreme environments. Numerous authors have addressed the energy available from a variety of inorganic sulfur redox pairs. Less attention has been paid, however, to the energy required or gained from metabolic reactions among organic sulfur compounds. Work in this area has focused on the oxidation of alkyl sulfide or disulfide to thiol and formaldehyde, e.g. (CH3)2S + H2O yields CH3SH + HCHO + H2, eventually resulting in the formation of CO2 and SO4(-2). It is also found that reactions among thiols and disulfides may help control redox disequilibria between the cytoplasm and the periplasm. Building on our earlier efforts for thiols, we have compiled and estimated thermodynamic properties for alkyl sulfides. We are investigating metabolic reactions among various sulfur compounds in a variety of extreme environments, ranging from sea floor hydrothermal systems to organic-rich sludge. Using thermodynamic data and the revised HKF equation of state, along with constraints imposed by the geochemical environments sulfur-metabolizing organisms inhabit, we are able to calculate the amount of energy available to these organisms.

Schulte, M.↗
NASA NTRS2004

Association between gravitational force and tissue metabolism in periparturient rats

Recently, interest in mammalian reproduction and offspring survival in altered gravity has been growing. Because successful lactation is critical for mammalian neonate survival, we have been studying the effect of gravity metabolism. We have shown an exponential relationship between glucose metabolic rate in mammary tissue of periparturient rats and an increase in gravity load. In this study we showed that changes in mammary metabolic rate due to gravity force were accompanied by a decrease in glucose metabolism in adipose tissue and by a reduced size of adipocytes. We assume that these changes are likely due to changes in prolactin or leptin levels related to altered gravity load.

NASA Discipline Developmental Biology↗
NASA NTRS2004

Redesign of the Human Metabolic Simulator

The National Aeronautics and Space Administration (NASA) is currently building a Human Metabolic Simulator (HMS) at the Johnson Space Center as part of the Advanced Life Support Air Revitalization Technology Evaluation Facility (ARTEF). The purpose of ARTEF is to evaluate Environmental Control and Life Support System Technologies for Advanced Missions. The HMS is needed to reproduce the primary metabolic effects of human respiration on an enclosed atmosphere when humans cannot be present and the impact of human presence on the system is required. A HMS was designed, built and successfully operated in 2000 but larger crew size requirements and the expense of upgrade of the current system necessitate redesign. This paper addresses the redesign. Several concepts were considered, ranging from chemical oxidation of a hydrocarbon like ethanol or ethyl acetate to carbon dioxide and water, oxidation of an iron-containing compound, or by using a fuel cell. For reasons of cost, simplicity, safety and other factors, the concept chosen includes: a molecular sieve packaged as an industrial oxygen concentrator to remove oxygen from the atmosphere, with direct carbon dioxide, water and heat injection. The water injection is done via heating water to steam with a heat exchanger and thermal effects are handled by directly adding heat to the air stream with a second heat exchanger. Both heat exchangers are supplied by a hot oil loop. The amount of oxygen removal, carbon dioxide addition, water addition and heat addition were calculated using metabolic profiles for respiration and heat, calculated using a series of empirical equations developed for International Space Station (ISS). Sketches of the Human Metabolic Simulator and the hot oil bath loop used to supply heat to the heat exchangers are included

Duffield, Bruce↗
NASA NTRS2007

Metabolic Heat Regenerated Temperature Swing Adsorption for CO(sub 2) and Heat Removal/Rejection in a Martian PLSS

Two of the fundamental problems facing the development of a Portable Life Support System (PLSS) for use on Mars, are (i) heat rejection (because traditional technologies use sublimation of water, which wastes a scarce resource and contaminates the premises), and (ii) rejection of CO2 in an environment with a ppCO2 of 0.4-0.9 kPa. Patent-pending Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed to address both these challenges. The technology utilizes an adsorbent that when cooled with liquid CO2 to near sublimation temperatures (~195K) removes metabolically-produced CO2 in the vent loop. Once fully loaded, the adsorbent is then warmed externally by the vent loop (approx. 300K), rejecting the captured CO2 to Mars ambient. Two beds are used to effect a continuous cycle of CO2 removal/rejection as well as facilitate heat exchange out of the vent loop. Any cryogenic fluid can be used in the application; however, since CO2 is readily available at Mars and can be easily produced and stored on the Martian surface, the solution is rather elegant and less complicated when employing liquid CO2. As some metabolic heat will need to be rejected anyway, finding a practical use for metabolic heat is also an overall benefit to the PLSS. To investigate the feasibility of the technology, a series of experiments was conducted which lead to the selection and partial characterization of an appropriate adsorbent. The adsorbent NaX successfully removed CO2 from a simulated vent loop at the prescribed temperature swing anticipated during PLSS operating conditions on Mars using a cryogenic fluid. Thermal conductivity of the adsorbent was also measured to eventually aid in a demonstrator design of the technology. These results provide no show stoppers to the development of MTSA technology and allow its development to focus on other design challenges as listed in the conclusions.

Iacomini, Christine↗
NASA NTRS2007

Metabolic Heat Regenerated Temperature Swing Adsorption for CO2 and Heat Removal/Rejection in a Martian PLSS

Two of the fundamental problems facing the development of a Portable Life Support System (PLSS) for use on Mars, are (i) heat rejection (because traditional technologies use sublimation of water, which wastes a scarce resource and contaminates the premises), and (ii) rejection of carbon dioxide (CO2) in an environment with a CO2 partial pressure (ppCO2) of 0.4-0.9 kPa. Patent-pending Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed to address both these challenges. The technology utilizes an adsorbent that when cooled with liquid CO2 to near sublimation temperatures (~195K) removes metabolically-produced CO2 in the ventilation loop. Once fully loaded, the adsorbent is then warmed externally by the ventilation loop (~300K), rejecting the captured CO2 to Mars ambient. Two beds are used to provide a continuous cycle of CO2 removal/rejection as well as facilitate heat exchange out of the ventilation loop. Any cryogenic fluid can be used in the application; however, since CO2 is readily available on Mars and can be easily produced and stored on the Martian surface, the solution is rather elegant and less complicated when employing liquid CO2. As some metabolic heat will need to be rejected anyway, finding a practical use for metabolic heat is also an overall benefit to the PLSS. To investigate the feasibility of the technology, a series of experiments were conducted which lead to the selection and partial characterization of an appropriate adsorbent. The Molsiv Adsorbents 13X 8x12 (also known as NaX zeolite) successfully removed CO2 from a simulated ventilation loop at the prescribed temperature swing anticipated during PLSS operating conditions on Mars using a cryogenic fluid. Thermal conductivity of the adsorbent was also measured to eventually aid in a demonstrator design of the technology. These results provide no show stoppers to the development of MTSA technology and allow its development to focus on other design challenges as listed in the conclusions section of this paper.

Iacomini, Christine↗
NASA NTRSDate not supplied

Combining Disparate Measures of Metabolic Rate During Simulated Spacewalks

Scientists from NASA's Extravehicular Activities (EVA) Physiology Systems and Performance Project help design space suits for future missions, during which astronauts are expected to perform EVA activities on the Lunar or Martian surface. During an EVA, an astronaut's integrated metabolic rate is used to predict how much longer the activity can continue and still provide a safe margin of remaining consumables. For EVAs in the Apollo era, NASA physicians monitored live data feeds of heart rate, O 2 consumption, and liquid cooled garment (LCG) temperatures, which were subjectively combined or compared to produce an estimate of metabolic rate. But these multiple data feeds sometimes provided conflicting estimates of metabolic rate, making real-time calculations of remaining time difficult for physician/monitors. Currently, designs planned for the Constellation Program EVAs utilize an automated, but largely heuristic methodology for incorporating the above three measurements, plus an additional one - CO 2 production, ignoring data that appears in conflict; however a more rigorous model-based approach is desirable. In this study, we show how principal axis factor analysis, in combination with OLS regression and LOWESS smoothing can be used to estimate metabolic rate as a data-driven weighted average of heart rate, O 2 consumption, LCG temperature data, and CO 2 production. Preliminary results suggest less sensitivity to occasional spikes in observed data feeds, and reasonable within-subject reproducibility when applied to subsequent tasks. These methods do not require physician monitoring and as such can be automated in the electronic components of future space suits. With additional validation, our models show promise for increasing astronaut safety, while reducing the need for and potential errors associated with human monitoring of multiple systems.

Alan H Feiveson↗
NASA NTRS2010

In Vitro Disease Model of Microgravity Conditioning on Human Energy Metabolism

NASA and its partners are committed to introducing appropriate new technology to enable learning and living safely beyond the Earth for extended periods of time in a sustainable and possibly indefinite manner. In the responsible acquisition of that goal, life sciences is tasked to tune and advance current medical technology to prepare for human health and wellness in the space environment. The space environment affects the condition and function of biological systems from organ level function to shape of individual organelles. The objective of this paper is to study the effect of microgravity on kinetics of drug metabolism. This fundamental characterization is meaningful to (1) scientific understanding of the response of biology to microgravity and (2) clinical dosing requirements and pharmacological thresholds during long term manned space exploration. Metabolism kinetics of the anti-nausea drug promethazine (PMZ) were determined by an in vitro ground model of 3-dimensional aggregates of human hepatocytes conditioned to weightlessness using a rotating wall bioreactor. The authors observed up-regulated PMZ conversion in model microgravity conditions and attribute this to effect to model microgravity conditioning acting on metabolic mechanisms of the cells. Further work is necessary to determine which particular cellular mechanisms are governing the experimental observations, but the authors conclude kinetics of drug metabolism are responsive to gravitational fields and further study of this sensitivity would improve dosing of pharmaceuticals to persons exposed to a microgravity environment.

Snyder, Jessica↗
NASA NTRS2016

Development of an Objective Space Suit Mobility Performance Metric Using Metabolic Cost and Functional Tasks

Existing methods for evaluating EVA suit performance and mobility have historically concentrated on isolated joint range of motion and torque. However, these techniques do little to evaluate how well a suited crewmember can actually perform during an EVA. An alternative method of characterizing suited mobility through measurement of metabolic cost to the wearer has been evaluated at Johnson Space Center over the past several years. The most recent study involved six test subjects completing multiple trials of various functional tasks in each of three different space suits; the results indicated it was often possible to discern between different suit designs on the basis of metabolic cost alone. However, other variables may have an effect on real-world suited performance; namely, completion time of the task, the gravity field in which the task is completed, etc. While previous results have analyzed completion time, metabolic cost, and metabolic cost normalized to system mass individually, it is desirable to develop a single metric comprising these (and potentially other) performance metrics. This paper outlines the background upon which this single-score metric is determined to be feasible, and initial efforts to develop such a metric. Forward work includes variable coefficient determination and verification of the metric through repeated testing.

Norcross, J. R.↗
NASA NTRS2016

Development of an Objective Space Suit Mobility Performance Metric Using Metabolic Cost and Functional Tasks

Existing methods for evaluating EVA suit performance and mobility have historically concentrated on isolated joint range of motion and torque. However, these techniques do little to evaluate how well a suited crewmember can actually perform during an EVA. An alternative method of characterizing suited mobility through measurement of metabolic cost to the wearer has been evaluated at Johnson Space Center over the past several years. The most recent study involved six test subjects completing multiple trials of various functional tasks in each of three different space suits; the results indicated it was often possible to discern between different suit designs on the basis of metabolic cost alone. However, other variables may have an effect on real-world suited performance; namely, completion time of the task, the gravity field in which the task is completed, etc. While previous results have analyzed completion time, metabolic cost, and metabolic cost normalized to system mass individually, it is desirable to develop a single metric comprising these (and potentially other) performance metrics. This paper outlines the background upon which this single-score metric is determined to be feasible, and initial efforts to develop such a metric. Forward work includes variable coefficient determination and verification of the metric through repeated testing.

McFarland, Shane M.↗
NASA NTRSDate not supplied

One-Carbon Metabolism and SANS 2022 Update

Spaceflight Associated Neuro-ocular Syndrome, or SANS, affects a subset of astronauts (1, 2), and biochemical evidence has documented differences in those astronauts (3). Specifically, they had higher circulating concentrations of metabolites of the one-carbon metabolic pathway (1C), including homocysteine, and these concentrations were higher before flight (3). After ruling out many potential confounding factors in these otherwise healthy individuals (e.g., sex, kidney function, vitamin status, coffee consumption), a study of genetics was warranted. In an initial pilot effort, we documented a genetic predisposition to develop ophthalmic changes after long-duration space flight (4). That is, from a limited study of 5 single-nucleotide polymorphisms (SNPs), we found that the G allele for the MTRR A66G SNP was associated with a greater risk of choroidal folds and cotton-wool spots after flight, and the C allele for SHMT1 C1420T was protective against optic disc edema (4). These data provide a potential pathway for understanding why some individuals develop SANS, while others do not. The initial pilot study of 5 SNPs yielded striking findings, but the 1C pathway is far more complex. An effort was undertaken to examine more than 500 1C SNPs to see if a broader examination could help illuminate this association. That work is ongoing. The astronaut findings led us to advocate for the inclusion of 1C pathway genetic and biochemistry testing on other SANS-related projects, noting that genetics might help identify responders, non-responders, or outliers. The first such effort yielded evidence of an association of specific forms of the MTRR and SHMT-1 SNPs and vitamin B12 status with end-tidal CO2 after acute carbon dioxide exposure (5). The second such effort led to the identification that individuals exposed to strict head-down tilt and CO2 for 30-d who developed optic disc edema also had risk alleles for the two SNPs described above (6). Additionally, we identified a clinical population with many characteristics either attributed or purported to be involved in the ocular changes seen in affected astronauts: women with polycystic ovary syndrome (PCOS). PCOS is a condition of androgen excess and anovulatory menstrual cycles. The shared characteristics and clinical findings between SANS and PCOS generally include higher circulating homocysteine concentrations, increased retinal nerve fiber layer thickness, increased androgen concentrations (or responses), and altered carbohydrate metabolism. To our knowledge, no study has examined whether women with PCOS have asymptomatic ophthalmic anomalies observed in astronauts with SANS. While researchers have evaluated the one-carbon metabolism pathway polymorphisms of PCOS patients, and initial studies show an association with certain one-carbon polymorphisms, none have looked at the set of SNPs identified in our studies that are associated with ophthalmic changes in astronauts. Accordingly, we designed a study to evaluate the association of one-carbon pathway SNPs and ophthalmic findings in patients with PCOS and/or IIH compared to controls. Subjects provided blood samples for vitamin and one carbon biochemistry analyses, an extensive analysis of >500 SNPs associated with one carbon metabolism and had eye examinations and ocular imaging. Data analysis are underway. The data collected to date have shown associations between one carbon pathway biochemistry and genetics and incidence of SANS. The mechanisms for SANS has yet to be identified, although many hypotheses exist. Based on our data, we have developed (8, 9) and expanded (6) a multi-hit hypothesis for how these seemingly disparate findings could be linked. While intriguing, the hypothesis represents the starting point for further research. We aim to clarify the relationship between B-vitamin status and genetics with regard to the risk of SANS. Ultimately, understanding the mechanism(s) behind this will provide a means to predict, prevent, or treat these ophthalmologic pathologies in astronauts, and terrestrial populations.

S M Smith↗
NASA NTRSDate not supplied

Microbial Optical Data Processing: A Key Step in the Metabolic Assessment of Lunar Explorer Instrument for Space Biology Applications (LEIA) and Biosentinel’s Payload Data

The BioSensor payload platform on BioSentinel and LEIA autonomously collects optical data from microbial model organisms in liquid culture. The BioSensor is designed to monitor metabolic activity using absorbance measurements of cell density and alamarBlue, a readily available colorimetric redox indicator dye. BioSentinel, a pioneering NASA CubeSat, uses yeast to study deep space radiation. LEIA investigates radiation and lunar gravity response. The experimental setup includes 16 wells equipped with three LEDs (570, 630, and 850 nm) and their corresponding photodetectors. One well is a calibration control without biology while the rest have desiccated cultures. Autonomous rehydration initiates the experiment. Data from the BioSensor are received from the flight and ground units, enabling comparison to uncover location-based metabolic rate variations. This study presents a Python Jupyter notebook developed for efficient data processing of multiple CSV files containing date and time columns, temperature, and well illumination data. It offers a user-friendly interface while maintaining computational power, automatically recognizing and iteratively processing data files in a user-input path. A Hampel filter with a short window eliminates outlier artifacts from sensor dropout. Because absorbance is a relative measurement, conversion from raw illumination requires defining a “blank” value, so the first data points are averaged to provide the necessary denominator. A cube-root function correction mitigates undesired drift caused by air pockets during the fluidic card filling phase, maintaining optical path length consistency. Beer-Lambert's law is applied to further convert absorbance values to cell and dye form concentrations, the desired science parameters. The processed data are saved and visualized as SVG plots. Future plans include extracting specific science parameters from the processed data like growth rate and metabolic rate, and identification of features corresponding to metabolic and phenotypic shifts such as starvation, shifts from aerobic to anaerobic growth, and osmotic stresses.

Space biology↗
NASA NTRS2024

Core Body Temperature Predictions Using Metabolic Energy Expenditure and Heart Rate During Simulated Extravehicular Activity

Long duration spaceflight missions will require crew to become more autonomous in conducting extravehicular activities (EVA) without direct communication with Mission Control for biomedical support. To enable such autonomy, we are developing a Crew State and Risk Model (CSRM) as a collection of key physiology domains that drive EVA crew capabilities and workloads. One model component of CSRM is human thermal regulation. In this paper, customized development of a baseline model to predict core body temperature is presented using physiology inputs of heart rate and metabolic rate. The model development dataset included a baseline study where participants (n=6, equal male and female) performed a 5-hour EVA in a two-part session while wearing a hybrid space suit simulator (HS3). The first session included an end-to-end EVA traversing 1500 meters to a geology site and traversing back to a habitat conducting geology, payload relocation, and maintenance operations every 500 meters. The second session included standalone tasks of a 2000-meter traverse followed by geology tasks. Thermal measures of core body temperature, local skin temperature, liquid cooling garment temperature, heart rate, and metabolic rate were collected through the test duration. Multiple regression was used to build a linear equation to predict core body temperature from inputs of heart rate and metabolic rate. Heat storage was calculated via predicted core body temperature plus LCG and skin temperatures. The model was tested against a dataset from a pressurized suited test (n=6, equal male and female) in the NASA Active Response Gravity Offload System (ARGOS) conducting similar end-to-end EVA and standalone tasks. Predicted error of the model against the raw test cases was 0.2±0.15 °C. The baseline prediction of core body temperature using heart rates and metabolic rates allows for simple real-time tracking from data collected in-flight to monitor crew consumables and thermal flight limits during EVA.

Bradley Hoffmann↗
DOE OSTI2026

Coarse-grained resource allocation modeling for decoding and rewiring microbial metabolism

Microbial metabolism is a complex, emergent system driven by the coordinated interplay of intricate and dynamic molecular processes. To elucidate cellular behavior and enable biotechnological applications, quantitative models that address the inherent complexity of metabolism have been developed from a resource allocation perspective. Here, we synthesize recent advances in coarse-grained resource allocation frameworks and their applications in understanding microbial physiology and guiding gene circuit design. Here, these frameworks reveal global regulatory constraints and predict cellular adaptation to nutrient and environmental changes. In addition, they enable the quantification of metabolic costs, the dissection of circuit–host interactions, and the development of strategies for burden mitigation. Collectively, these modeling frameworks provide a powerful platform for uncovering quantitative principles of microbial growth and engineering robust synthetic biological systems.

coarse-grained modeling↗
DOE OSTI2025

Feedstock-efficient conversion through hydrogen and formate-driven metabolism in Escherichia coli

Product yields for biomanufacturing processes are often constrained by the tight coupling of cellular energy generation and carbon metabolism in sugar-based fermentation systems. To overcome this limitation, we engineered Escherichia coli to utilize hydrogen gas (H 2 ) and formate (HCOO - ) as alternative sources of energy and reducing equivalents, thereby decoupling energy generation from carbon metabolism. This approach enabled precise suppression of decarboxylative oxidation during acetate growth, with 86.6 ± 1.6 % of electrons from hydrogen gas (via soluble hydrogenase from Cupriavidus necator H16) and 98.4 ± 3.6 % of electrons from formate (via formate dehydrogenase from Pseudomonas sp. 101) offsetting acetate oxidation. Hydrogen gas supplementation led to a titratable and stoichiometric reduction in CO 2 evolution in acetate-fed cultures. Metabolomic analysis suggests that this metabolic decoupling redirects carbon flux through the glyoxylate shunt, partially bypassing two decarboxylative steps in the TCA cycle. Here, we demonstrated the utility of this strategy by applying it to mevalonate biosynthesis, where formate supplementation during glucose fermentation increased titers by 57.6 % in our best-performing strain. Flux balance analysis further estimated that 99.0 ± 2.8 % of electrons from formate were used to enhance mevalonate production. These findings highlight a broadly applicable strategy for enhancing biomanufacturing efficiency by leveraging external reducing power to optimize feedstock and energy use.

Biomanufacturing↗
DOE OSTI2024

Advances in Engineering Nucleotide Sugar Metabolism for Natural Product Glycosylation in Saccharomyces cerevisiae

Glycosylation is a ubiquitous modification present across all of biology, affecting many things such as physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Nucleotide sugars are important precursors needed to study glycosylation and produce glycosylated products. Saccharomyces cerevisiae is a potentially powerful platform for producing glycosylated biomolecules, but it lacks nucleotide sugar diversity. Nucleotide sugar metabolism is complex, and understanding how to engineer it will be necessary to both access and study heterologous glycosylations found across biology. This review overviews the potential challenges with engineering nucleotide sugar metabolism in yeast from the salvage pathways that convert free sugars to their associated UDP-sugars to de novo synthesis where nucleotide sugars are interconverted through a complex metabolic network with governing feedback mechanisms. Finally, recent examples of engineering complex glycosylation of small molecules in S. cerevisiae are explored and assessed.

59 BASIC BIOLOGICAL SCIENCES↗