Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “toxicity prediction”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Inhibition of Chromium(III) Oxidation through Manganese(IV) Oxide Passivation and Iron(II) Abiotic Reduction

Manganese (Mn) oxides are strong oxidants that are ubiquitous in soils and can oxidize redox-active metals, including chromium (Cr). In soil environments, trivalent chromium (Cr(III)) is a benign, immobile micronutrient, whereas the hexavalent Cr(VI) form is present as a highly mobile, toxic chromate oxyanion. Although many studies have characterized the capacity of Mn(III/IV) oxides to oxidize Cr(III) to toxic Cr(VI), the oxidative capacity of Mn oxides in the presence of potentially passivating soil constituents, specifically reduced soluble iron (Fe(II) aq ), remains unresolved. We hypothesized that chemical processes at redox interfaces, such as diffusion-limited environments within soil aggregates, can lead to decreased Cr(VI) production from Mn oxide-driven oxidation due to passivation by Fe(II) aq . A multichamber diffusion-limited reactor was used to simulate transport at soil redox interfaces and investigate the capacity of poorly crystalline and crystalline Mn oxides to oxidize solid Cr(III) minerals to Cr(VI) in the presence of Fe(II) aq . As predicted, Cr(VI) was produced through the Mn oxide-catalyzed oxidation of Cr(III) at a rate controlled by the solubility of Cr(OH) 3 . However, in the presence of Fe(II) aq , the concentration of aqueous Cr(VI) decreased as a function of the Fe(II) aq concentration, where high concentrations of Fe(II) aq completely inhibited Cr(VI) production, likely through both the passivation of the Mn oxide and the direct reduction of Cr(VI) by Fe(II). At both low (14 μM) and high (100 μM) Fe(II) aq concentrations, the iron oxide minerals hematite (Fe 2 O 3 ) and goethite (α-FeOOH) were associated with the Mn oxides, which can cause surface passivation, a likely role that decreases Cr(III) oxidation. Additionally, the Cr(III) oxidation rate decreased with increasing crystallinity of the Mn oxides whether or not Fe(II) was present.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Trace metal transfer to passerines inhabiting wastewater treatment wetlands

Wastewater treatment wetlands are cost-effective strategies for remediating trace metals in industrial effluent. However, biogeochemical exchange between wastewater treatment wetlands and adjacent environments provides opportunities for trace metals to cycle in surrounding ecosystems. The transfer of trace metals to wildlife inhabiting treatment wetlands must be considered when evaluating wetland success. Using passerine birds as bioindicators, we conducted a multi-tissue analysis to investigate the mobilization of zinc, copper, and lead derived from wastewater to terrestrial wildlife in treatment wetlands and surrounding habitat. In addition, we evaluate the strength of relationships between metal concentrations in non-lethal (blood and feathers) and lethal (muscle and liver) sample types for estimation of toxicity risk. From July 2020 to August 2021, 177 passerines of seven species were captured at two wetlands constructed to treat industrial wastewater and two reference wetlands in the coastal plain of South Carolina. Feather, blood, liver, and muscle samples from each bird were analyzed for fourteen metals using inductively coupled plasma mass spectrometry and direct mercury analysis. Passerines inhabiting wastewater treatment wetlands accumulated higher concentrations of zinc in liver, copper in blood, and lead in feathers than passerines in reference wetlands, but neither blood nor feather concentrations were correlated with internal tissue concentrations. Of all the detected metals, only mercury in the blood showed a strong predictive relationship with mercury in internal tissues. This study indicates that trace metals derived from wastewater are bioavailable and exported to terrestrial wildlife and that passerine biomonitoring is a valuable tool for assessing metal transfer from treatment wetlands. Furthermore, regular blood sampling can reveal proximate trace metal exposure but cannot predict internal body burdens for most metals.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
NASA NTRS2019

Vapor Growth of Indium Monoiodide

Indium (I) iodide, InI, is part of a group of heavy metal iodides that can be used as room temperature radiation detectors. Other examples are HgI2, PbI2, BiI3, or TlPbI3. InI has several advantages, such as low toxicity, no solid phase transition (such as in HgI2), and no tendency to form polytypes (PbI2, BiI3 ). All binary iodides have layered structures and are quite soft, but InI is also the mechanically most stable compound of the binary compounds. Table 1 shows the main properties of InI in comparison with the other iodides and the most common room temperature radiation detector material, (Cd, Zn)Te. InI is typically grown by the unseeded Bridgman method using a nucleation tip, but Czochralski (CZ) growth has also been demonstrated. The resulting crystals have been used successfully for radiation detection, but both resistivity and mobility are usually well below theoretically predicted values. Physical vapor transport (PVT), although much slower than melt growth, is an alternative method and has been used to grow e.g. HgI2, PbI2, BiI3, CdTe. PVT growth should eliminate or reduce inclusions and impurities since it is based on sublimation, reduce intrinsic defects due to the lower growth temperature, and reduce dislocation densities due to reduced thermal and mechanical stress. As an example, PVT-grown CdTe showed a much improved structural quality compared to Bridgman- or THM-grown material.

Cröll, Arne↗
DOE OSTI2024

Automated AI-driven Molecular Design for Therapeutic Discovery

In recent years, artificial intelligence and machine learning (AI/ML) approaches have revolutionized the process of designing new therapeutics, enabling scientists to rapidly respond to emerging threats from various pathogens. A prime example is the SARS-CoV-2 main protease, a key target for the development of antiviral inhibitors. In this study, we employed a novel, integrated approach that combines AI-driven iterative design of inhibitor candidates, screening based on physio-chemical properties and toxicity, physics-based computational modeling of protein-inhibitor interactions, and AI-assisted analysis of Native MS biophysical assay and characterization of designed candidates. Our deep learning 3D-scaffold model, which uses an input scaffold as a starting point, generated tens of thousands of compounds while preserving the key scaffold. To optimize these candidates, we calculated a comprehensive set of 136 descriptors, including both 2D and 3D molecular features, for compounds targeting the SARS-CoV-2 Main protease (Mpro) and a neurodegenerative disease-associated protein, cyclophilin (Cyp). The generated compounds were initially filtered based on their properties and then ranked according to their predicted binding affinity using our automated modeling and ML methods. Experimental validation of the Mpro candidates showing inhibitory activity demonstrates that our workflow can expedite the therapeutic discovery.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1992

Development of microcomputer-based mental acuity tests

Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.

Non-NASA Center↗
DOE OSTI2025

A small number of point mutations confer formate tolerance in Shewanella oneidensis

ABSTRACT Microbial electrosynthesis (MES) is a sustainable approach to chemical production from CO 2 and clean electricity. However, limitations in electron transfer efficiency and gaps in understanding of electron transfer pathways in MES systems prevent full realization of this technology. Shewanella oneidensis could serve as an MES biocatalyst because it has a well-studied, efficient transmembrane electron transfer pathway. A key first step in MES in this organism could be CO 2 reduction to formate. However, we report that wild-type S. oneidensis does not tolerate high levels of formate. In this work, we created and characterized formate-tolerant strains of S. oneidensis for further engineering and future use in MES systems through adaptive laboratory evolution. Two different point mutations in a gene encoding a predicted sodium-dependent bicarbonate transporter and a DUF2721-containing protein separately confer formate tolerance to S. oneidensis . The mutations were further evaluated to understand their role in improving formate tolerance. We also show that the wild-type and mutant versions of the putative sodium-dependent bicarbonate transporter improve formate tolerance of Zymomonas mobilis , indicating the potential of transferring this formate tolerance phenotype to other organisms. IMPORTANCE Shewanella oneidensis is a bacterium with a well-studied, efficient extracellular electron transfer pathway. This capability could make this organism a suitable host for microbial electrosynthesis using CO 2 or formate as feedstocks. However, we report here that formate is toxic to S. oneidensis , limiting the potential for its use in these systems. In this work, we evolve several strains of S. oneidensis that have improved formate tolerance, and we investigate some mutations that confer this phenotype. The phenotype is confirmed to be attributed to several single point mutations by transferring the wild-type and mutant versions of each gene to the wild-type strain. Finally, the formate tolerance mechanism of one variant is studied using structural modeling and expression in another host. This study, therefore, presents a simple method for conferring formate tolerance to bacterial hosts.

Cross, Megan C. Gruenberg (ORCID:0000000291589900)↗
DOE OSTI2023

Quality Assurance Project Plan for the Salish Sea Model – Continuing Development of New Capabilities and Applications: European Green Crab (EGC) Larval Transport, Coupling to VELMA and Atlantis, Performance Improvements and Diagnostic Applications

This quality assurance project plan (QAPP) is for proposed FY24-FY27 efforts to (a) develop/expand a predictive European Green Crab (EGC) larval dispersal model for the Salish Sea, (b) add linkage between VELMA (Visualizing Ecosystem Land Management Assessments) watershed model and Atlantis model (ecosystem dynamics and food web) through SSM, and (c) continue SSM capability development through the addition of metals, harmful algal blooms (HABs), and FVCOM-LTRANS (Lagrangian Larval Transport) modules.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Development of Metal-Free Photocatalysts

Solar fuels show great promise as clean, sustainable energy sources; however, established technologies are still plagued by high price, toxicity concerns, or low efficiencies. There is a critical need for inexpensive, benign materials that can effectively harness the sun’s energy. The overarching objective of this project is to evaluate the compatibility of novel material combinations for use as metal-free, heterojunction photocatalysts. Our central hypothesis is that by tuning the electronic structure of individual components in hybrid composites, via selective chemical modifications and physical stimuli to the interface, we can improve the photocatalytic properties of the overall assembly. We will determine factors that affect energy band gaps and band edge positions in isolated photocatalyst systems as well as explore routes to modulate heterojunction band alignments in composite assemblies. Our results will predict accessible pathways for charge carriers in new composite photocatalysts, facilitating access to more of the solar spectrum via inexpensive, environmentally-friendly material combinations.

14 SOLAR ENERGY↗
NASA NTRS2000

The Evolution of Sulfide Tolerance in the Cyanobacteria

Understanding how the function of extant microorganisms has recorded both their evolutionary histories and their past interactions with the environment is a stated goal of astrobiology. We are taking a multidisciplinary approach to investigate the diversification of sulfide tolerance mechanisms in the cyanobacteria, which vary both in their degree of exposure to sulfide and in their capacity to tolerate this inhibitor of photosynthetic electron transport. Since conditions were very reducing during the first part of Earth's history and detrital sulfides have been found in Archean sediments, mechanisms conferring sulfide tolerance may have been important for the evolutionary success of the ancestors of extant cyanobacteria. Two tolerance mechanisms have been identified in this group: (1) resistance of photosystem II, the principal target of sulfide toxicity; and (2) maintenance of the ability to fix carbon despite photosystem II inhibition by utilizing sulfide as an electron donor in photosystem I - dependent, anoxygenic photosynthesis. We are presently collecting comparative data on aspects of sulfide physiology for laboratory clones isolated from a variety of habitats. These data will be analyzed within a phylogenetic framework inferred from molecular sequence data collected for these clones to test how frequently different mechanisms of tolerance have evolved and which tolerance mechanism evolved first. In addition, by analyzing these physiological data together with environmental sulfide data collected from our research sites using microelectrodes, we can also test whether the breadth of an organism's sulfide tolerance can be predicted from the magnitude of variation in environmental sulfide concentration it has experienced in its recent evolutionary past and whether greater average sulfide concentration and/or temporal variability in sulfide favors the evolution of a particular mechanism of sulfide tolerance.

Miller, Scott R.↗
DOE OSTI2023

Automated bidirectional coupling of multiscale models of aerosol dosimetry: Validation with subject-specific deposition data

Assessing the toxicity of airborne particulate matter or the efficacy of inhaled drug depends upon accurate estimates of deposited fraction of inhaled materials. In silico approaches can provide important insights into site- or airway-specific deposition of inhaled aerosols in the respiratory system. In this study, we improved on our recently developed 3D/1D model that simulate aerosol transport and deposition in the whole lung over multiple breath cycles. A subject-specific multiscale lung model of a healthy male subject using computational fluid-particle dynamics (CFPD) in a 3D model of the oral cavity through the large bronchial airways entering each lobe was bidirectionally coupled with a recently improved Multiple Path Particle Dosimetry (MPPD) model to predict aerosol deposition over the entire respiratory tract over multiple breaths for four conditions matching experimental aerosol exposures in the same subject from which the model was developed. These include two particle sizes (1 and 2.9 μm) and two subject-specific breathing rates of ~300 ml/s (slow breathing) and ~750 ml/s (fast breathing) at a target tidal volume of 1 L. In silico predictions of retained fraction were 0.31 and 0.29 for 1 μm and 0.66 and 0.62 for 2.9 μm during slow and fast breathing, respectively, and compared well with experimental data (1 μm: 0.31 ± 0.01 (slow) and 0.27 ± 0.01 (fast), 2.9 μm: 0.63 ± 0.03 (slow) and 0.68 ± 0.02 (fast)). Furthermore, these results provide a great deal of confidence in the validity and reliability of our approach.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

Low Intensity Low Temperature (LILT) measurements and coefficients on new photovoltaic structures

Past NASA missions to Mars, Jupiter, and the outer planets were powered by radioisotope thermal generators (RTG's). Although these devices proved to be reliable, their high cost and highly toxic radioactive heat source has made them far less desirable for future planetary missions. This has resulted in a renewed search for alternate energy sources, some of them being photovoltaic (PV) and thermophotovoltaic (TPV). Both of these alternate energy sources convert light/thermal energy directly into electricity. In order to create a viable PV and TPV data base for planetary mission planners and cell designers, we have compiled low temperature low intensity (LILT) I-V data on single junction and multi-junction high efficiency solar cells. The cells tested here represent the latest photovoltaic technology. Using this LILT data to calculate dI(sub SC)/dT, dV(sub OC)/dT, dFF/dT, and also as a function of intensity, an accurate prediction of cell performance under the AMO spectrum can be determined. When combined with QUantum efficiency at Low Temperature (QULT) data, one can further enhance the data by adding spectral variations to the measurements. This paper presents an overview of LILT measurements and is only intended to be used as a guideline for material selection and performance predictions. As single junction and multi-junction cell technologies emerge, new test data must be collected. Cell materials included are Si, GaAs/Ge, GainP/GaAs/Ge, InP, InGaAs/InP, InP/InGaAs/InP, and GainP. Temperatures range as low as -175 C and intensities range from 1 sun to .02 suns.

Schelman, David A.↗
NASA NTRSDate not supplied

Supply and Resource Management to Progressively Enable EIMO

BACKGROUND: Current medical operations in Low Earth Orbit (LEO) allow for real-time audio-video communication with a flight surgeon at mission control, resupply, and medical evacuation to earth on the order of hours. As mission profiles change from LEO to the Moon, Mars, and beyond, medical risk as a contribution to overall mission risk is anticipated to rise substantially. Concurrently, due to the distance, the medical systems on board vehicles proposed for these mission types are expected to have reduced mass and volume allocation. Together, astronaut crews will be at a higher risk of major medical events, be required to perform a broader set of tasks, and have substantially reduced resources and support to do so. Earth Independent Medical Operations (EIMO) aims to identify and fill the gaps present in this progressively changing paradigm. OVERVIEW: Medical supplies, resources, and skills are central to spaceflight medical systems. Vehicles used for non-LEO missions are anticipated to be smaller and thus the medical system will also need to have reduced mass, volume, and power. Medical resources are another form of consumable and may need resupply or pre-deployment to meet crew needs. One particular concern is the degradation of medications which become less efficacious and potentially toxic with time, particularly given environmental conditions such as temperature, humidity, oxygen, and radiation which have not yet been fully studied. Supply and resource management in LEO is dependent on resupply, however the supply chain of transporting equipment does not yet have a clear infrastructure for missions beyond LEO. DISCUSSION: EIMO is intended to systemically identify and fill these gaps with forward-looking solutions. In mission monitoring of resources with technology like RFID, improving medical resource longevity, targeted resupply and careful pre-mission planning will be central to facilitate crew health and performance. One approach to optimizing resources is the Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) tool, which uses probabilistic risk assessment (PRA) to quantitatively predict medical risk and identify resources and skills that mitigate this risk. This evidence based, quantitative analysis prediction tool and several other approaches to meeting the challenge of supply and resource management are discussed.

Arian Anderson↗
NASA NTRS1984

A dynamic model for plant growth: validation study under changing temperatures

A dynamic simulation model to describe vegetative growth of plants, for which some functions and parameter values have been estimated previously by optimization search techniques and numerical experimentation based on data from constant temperature experiments, is validated under conditions of changing temperatures. To test the predictive capacity of the model, dry matter accumulation in the leaves, stems, and roots of tobacco plants (Nicotiana tabacum L.) was measured at 2- or 3-day intervals during a 5-week period when temperatures in controlled-environment rooms were programmed for changes at weekly and daily intervals and in ascending or descending sequences within a range of 14 to 34 degrees C. Simulations of dry matter accumulation and distribution were carried out using the programmed changes for experimental temperatures and compared with the measured values. The agreement between measured and predicted values was close and indicates that the temperature-dependent functional forms derived from constant-temperature experiments are adequate for modelling plant growth responses to conditions of changing temperatures with switching intervals as short as 1 day.

NASA Discipline Number 60-40↗
NASA NTRS1995

Low Intensity Low Temperature (LILT) Measurements and Coefficients on New Photovoltaic Structures

Past NASA missions to Mars, Jupiter and the outer planets were powered by radioisotope thermal generators (RTGs). Although these devices proved to be reliable, their high cost and highly toxic radioactive heat source has made them far less desirable for future planetary missions. This has resulted in a renewed search for alternate energy sources, some of them being photovoltaics (PV) and thermophotovoltaics (TPV). Both of these alternate energy sources convert light/thermal energy directly into electricity. In order to create a viable PV data base for planetary mission planners and cell designers, we have compiled low intensity low temperature (LILT) I-V data on single junction and multi-junction high efficiency solar cells. The cells tested here represent the latest photovoltaic technology. Using this LILT data to calculate Short Circuit Current (I(sub sc)), Open Circuit Voltage (V(sub os)), and Fill Factor (FF) as a function of temperature and intensity, an accurate prediction of cell performance under the AM0 spectrum can be determined. When combined with QUantum efficiency at Low Temperature (QULT) data, one can further enhance the data by adding spectral variations to the measurements. This paper presents an overview of LILT measurements and is only intended to be used as a guideline for material selection and performance predictions. As single junction and multi-junction cell technologies emerge, new test data must be collected. Cell materials included are Si, GaAs/Ge, GaInP/GaAs/GaAs, InP, InGaAs/InP, InP/InGaAs/InP, and GaInP. Temperatures range down to as low as -180 C and intensities range from 1 sun down to 0.02 suns. The coefficients presented in this paper represent experimental results and are intended to provide the user with approximate numbers.

Scheiman, David A.↗
DOE OSTI2022

Flux balance analysis of the ammonia-oxidizing bacterium Nitrosomonas europaea ATCC19718 unravels specific metabolic activities while degrading toxic compounds

The ammonia-oxidizing bacterium Nitrosomonas europaea has been widely recognized as an important player in the nitrogen cycle as well as one of the most abundant members in microbial communities for the treatment of industrial or sewage wastewater. Its natural metabolic versatility and extraordinary ability to degrade environmental pollutants (e.g., aromatic hydrocarbons such as benzene and toluene) enable it to thrive under various harsh environmental conditions. Constraint-based metabolic models constructed from genome sequences enable quantitative insight into the central and specialized metabolism within a target organism. These genome-scale models have been utilized to understand, optimize, and design new strategies for improved bioprocesses. Reduced modeling approaches have been used to elucidate Nitrosomonas europaea metabolism at a pathway level. However, genome-scale knowledge about the simultaneous oxidation of ammonia and pollutant metabolism of N . europaea remains limited. Here, we describe the reconstruction, manual curation, and validation of the genome-scale metabolic model for N . europaea , i GC535. This reconstruction is the most accurate metabolic model for a nitrifying organism to date, reaching an average prediction accuracy of over 90% under several growth conditions. The manually curated model can predict phenotypes under chemolithotrophic and chemolithoorganotrophic conditions while oxidating methane and wastewater pollutants. Calculated flux distributions under different trophic conditions show that several key pathways are affected by the type of carbon source available, including central carbon metabolism and energy production.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Nanoscale structure of a hybrid aqueous–nonaqueous electrolyte

A new class of electrolytes have been reported, hybridizing aqueous with non-aqueous solvents, which combines non-flammability and non-toxicity characteristics of aqueous electrolytes with the superior electrochemical stability of non-aqueous systems. Here, we report measurements of the structure of an electrolyte composed of an equal-mass mixture of 21 m LiTFSI-water and 9 m LiTFSI-dimethyl carbonate using high-energy x-ray diffraction and polarized neutron diffraction with isotope substitution. Neutron structure factors from partially and fully deuterated samples exhibit peaks at low scattering vector Q that we ascribe to long-range correlations involving both solvent molecules and TFSI − anions. Here we compare both sets of measurements with results of molecular dynamics simulations based on a polarizable force field. The structures derived from simulations are generally in agreement with those measured, except that neutron structure factors predicted for two partially deuterated samples show very intense scattering increasing up to the low- Q limit of simulation, indicating a partial segregation between the two solvents not observed in experimental measurements.

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

Translating dosimetry of Dibenzo[ def,p ]chrysene (DBC) and metabolites across dose and species using physiologically based pharmacokinetic (PBPK) modeling

We report that Dibenzo[def,p]chrysene (DBC) is an environmental polycyclic aromatic hydrocarbon (PAH) that causes tumors in mice and has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Animal toxicity studies often utilize higher doses than are found in relevant human exposures. Additionally, like many PAHs, DBC requires metabolic bioactivation to form the ultimate toxicant, and species differences in DBC and DBC metabolite metabolism have been observed. To understand the implications of dose and species differences, a physiologically based pharmacokinetic model (PBPK) for DBC and major metabolites was developed in mice and humans. Metabolism parameters used in the model were obtained from experimental in vitro metabolism assays using mice and human hepatic microsomes. PBPK model simulations were evaluated against mice dosed with 15 mg/kg DBC by oral gavage and human volunteers orally microdosed with 29 ng of DBC. DBC and its primary metabolite DBC-11,12-diol were measured in blood of mice and humans, while in urine, the majority of DBC metabolites were obeserved as conjugated DBC-11,12-diol, conjugated DBC tetrols, and unconjugated DBC tetrols. The PBPK model was able to predict the time course concentrations of DBC, DBC-11,12-diol, and other DBC metabolites in blood and urine of human volunteers and mice with reasonable accuracy. Agreement between model simulations and measured pharmacokinetic data in mice and human studies demonstrate the success and versatility of our model for interspecies extrapolation and applicability for different doses. Furthermore, our simulations show that internal dose metrics used for risk assessment do not necessarily scale allometrically, and that PBPK modeling provides a reliable approach to appropriately account for interspecies differences in metabolism and physiology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Enzymatic carbon–fluorine bond cleavage by human gut microbes

Fluorinated compounds are used for agrochemical, pharmaceutical, and numerous industrial applications, resulting in global contamination. In many molecules, fluorine is incorporated to enhance the half-life and improve bioavailability. Fluorinated compounds enter the human body through food, water, and xenobiotics including pharmaceuticals, exposing gut microbes to these substances. The human gut microbiota is known for its xenobiotic biotransformation capabilities, but it was not previously known whether gut microbial enzymes could break carbon-fluorine bonds, potentially altering the toxicity of these compounds. Here, through the development of a rapid, miniaturized fluoride detection assay for whole-cell screening, we identified active gut microbial defluorinases. We biochemically characterized enzymes from diverse human gut microbial classes including Clostridia, Bacilli, and Coriobacteriia, with the capacity to hydrolyze (di)fluorinated organic acids and a fluorinated amino acid. Whole-protein alanine scanning, molecular dynamics simulations, and chimeric protein design enabled the identification of a disordered C-terminal protein segment involved in defluorination activity. Domain swapping exclusively of the C-terminus conferred defluorination activity to a nondefluorinating dehalogenase. To advance our understanding of the structural and sequence differences between defluorinating and nondefluorinating dehalogenases, we trained machine learning models which identified protein termini as important features. Models trained on 41-amino acid segments from protein C termini alone predicted defluorination activity with 83% accuracy (compared to 95% accuracy based on full-length protein features). This work is relevant for therapeutic interventions and environmental and human health by uncovering specificity-determining signatures of fluorine biochemistry from the gut microbiome.

Probst, Silke I↗