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At least 613 records · Page 34
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

32.9% Efficient Tandem Solar Cell with Strain-Balanced GaInAs/GaAsP Quantum Wells: Preprint

We demonstrate single and dual junction solar cells with up to 80 strain-balanced GaInAs/GaAsP quantum wells (QWs), in order to extend the range of photon absorption. The net average stress in the quantum well layers is =12 MPa, despite coherent stresses in the individual layers that are 35-70 times greater. The GaAs-QW cell has a certified efficiency of (27.2 ± 0.2)% at one-sun; the GaInP/GaAs-QW tandem has a certified record one-sun efficiency of (32.9 ± 0.5)%. We will discuss the architecture of the devices, the physics behind the high performance, and pathways to further improvement.

GaAsP↗
DOE OSTI2020

Structural Changes and Reversibility Upon Deintercalation of Li from LiCoPO 4 Derivatives

In an effort to improve the cycle life and rate capability of olivine LiCoPO 4 , Cr, Fe, and Si were added to produce nominal Li 1.025 Co 0.84 Fe 0.10 Cr 0.05 Si 0.01 (PO 4 ) 1.025 . This cathode material has an energy density comparable to LiCoPO 4 , with markedly improved electrochemical performance. Here, we apply operando X-ray diffraction to gain an understanding of the crystallographic delithiation mechanism of this new substituted electrode material, compared to both LiCo 0.75 Fe 0.25 PO 4 and LiCo 0.75 Fe 0.25 PO 4 . Throughout charging, the extent of solid-solution domains was significantly increased in Li 1.025 Co 0.84 Fe 0.10 Cr 0.05 Si 0.01 (PO 4 ) 1.025 and LiCo 0.75 Fe 0.25 PO 4 compared to LiCoPO 4 . These domains reduce the mechanical strain during electrode function, providing a clear explanation for the high durability with Co substitution. Li 1.025 Co 0.84 Fe 0.10 Cr 0.05 Si 0.01 (PO 4 ) 1.025 operated at notably higher average potential than LiCo 0.75 Fe 0.25 PO 4 , which would increase the energy density of the cell. Ex situ measurements reveal the persistence of structural irreversibilities in the substituted phase after the first cycle, identifying avenues for further improvement in durability. Overall, this finding sheds light on the strategies for judicious cation substitution in LiCoPO 4 electrodes to maximize the cycle life while preserving high energy density, especially compared to LiFePO 4 .

25 ENERGY STORAGE↗
DOE OSTI2024

Algal Biomass Production via Open Pond Algae Farm Cultivation: 2023 State of Technology and Future Research

The annual State of Technology (SOT) assessment is an essential activity for platform research conducted under the Bioenergy Technologies Office (BETO). It allows for the impact of research progress (both directly achieved in-house at the National Renewable Energy Laboratory [NREL] and furnished by partner organizations) to be quantified in terms of economic improvements in the overall biofuel production process for a particular biomass processing pathway, whether based on terrestrial or algal biomass feedstocks. As such, initial benchmarks can be established for currently demonstrated performance, and progress can be tracked toward out-year goals to ultimately demonstrate economically viable biofuel technologies. NREL's algae SOT benchmarking efforts historically focused both on front-end algal biomass production and separately on back-end conversion to fuels through NREL's "combined algae processing" (CAP) pathway. The production model is based on outdoor long-term cultivation data, enabled by comprehensive algal biomass production trials conducted under the Development of Integrated Screening, Cultivar Optimization, and Verification Research (DISCOVR) consortium efforts, driven by data furnished by Arizona State University (ASU) at the Arizona Center for Algae Technology and Innovation (AzCATI) testbed site. The CAP model is based on experimental efforts conducted primarily under NREL research and development projects. This report focuses on front-end algal biomass production, documenting the pertinent algal biomass cultivation parameters that were input to the NREL open pond algae farm model. Through partnerships under DISCOVR, collaborators at ASU furnished details on cultivation performance metrics including biomass productivity and harvest densities for recent growth trials done at the AzCATI site. The resulting biomass productivity was calculated at 16.7 g/m 2 /day (ash-free dry weight [AFDW], annual average) for seasonal cultivation of Picochlorum celeri TG2 and Monoraphidium minutum 26B-AM biomass strains at the ASU site. Picochlorum celeri achieved the best productivity from April to September, with Monoraphidium minutum 26B-AM being used between October and March. Tetraselmis striata LANL1001, usually part of the strain rotation in previous cultivation SOTs, was supplanted by Monoraphidium minutum 26B-AM in this year's outdoor cultivation trials. Finally, building from an industry case study presented in the 2022 SOT report, in the Appendix of this report we provide an update on further improved data furnished by an industry collaborator and resultant impacts on economics reflecting several seasonal scenarios. This case study provides a supplementary datapoint on work being performed elsewhere with a more dedicated focus on improved compositional quality, producing biomass enriched in lipids as may be more optimal for conversion upgrading to fuels and products.

09 BIOMASS FUELS↗
DOE OSTI2022

A Chromosome-Scale Genome Assembly of a Helicoverpa zea Strain Resistant to Bacillus thuringiensis Cry1Ac Insecticidal Protein

Helicoverpa zea (Lepidoptera: Noctuidae) is an insect pest of major cultivated crops in North and South America. The species has adapted to different host plants and developed resistance to several insecticidal agents, including Bacillus thuringiensis (Bt) insecticidal proteins in transgenic cotton and maize. Helicoverpa zea populations persist year-round in tropical and subtropical regions, but seasonal migrations into temperate zones increase the geographic range of associated crop damage. To better understand the genetic basis of these physiological and ecological characteristics, we generated a high-quality chromosome-level assembly for a single H. zea male from Bt-resistant strain, HzStark_Cry1AcR. Hi-C data were used to scaffold an initial 375.2 Mb contig assembly into 30 autosomes and the Z sex chromosome (scaffold N50 = 12.8 Mb and L50 = 14). The scaffolded assembly was error-corrected with a novel pipeline, polishCLR. The mitochondrial genome was assembled through an improved pipeline and annotated. Assessment of this genome assembly indicated 98.8% of the Lepidopteran Benchmark Universal Single-Copy Ortholog set were complete (98.5% as complete single copy). Repetitive elements comprised approximately 29.5% of the assembly with the plurality (11.2%) classified as retroelements. This chromosome-scale reference assembly for H. zea, ilHelZeax1.1, will facilitate future research to evaluate and enhance sustainable crop production practices.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Chapter 16: Connecting Microbial Genotype with Phenotype in the Omics Era

Although rational design-based metabolic engineering has been applied widely to obtain promising microbial biocatalysts, conventional strategies such as adaptive laboratory evolution (ALE) and mutagenesis are still efficient approaches to improve microorganisms for exceptional features such as a broad spectrum of substrate utilization, robustness of cell growth, as well as high titer, yield, and productivity of the target products. In this chapter, we describe the procedure to generate mutant strains with desired phenotypes using ALE and a new mutagenesis approach of Atmosphere and Room Temperature Plasma (ARTP). In addition, we discuss the methodology to combine next-generation sequencing (NGS)-based genome-resequencing and RNA-Seq transcriptomics approaches to characterize the mutant strains and connect the phenotypes with their corresponding genotypic changes.

adaptive laboratory evolution (ALE)↗
DOE OSTI2023

In-situ measurement and control of the tool-workpiece interface temperature during friction stir processing of 304/304L stainless steel

Friction stir processing of 304/304L stainless steel is an area of interest for repair of spent nuclear fuel canisters. To enable repair without canister deflection or fracture, it is necessary to define the limitations for the depth of the processing zone which will be critically dependent on the thermal history of the material. Here, this work provides the first direct measurement of the interface temperature for friction stir processing of steel. The measured temperature is in the range of 850–1050 °C which is 20–30 % higher than previously reported values. Notably, the peak temperature occurs at the pin tip which is attributed to a higher sticking fraction and subsequently higher strain rate near the tool axis of rotation. Furthermore, a clear correlation between the temperature, grain size, and hardness is established within a single weld nugget and across different processing conditions. In the future, this data may lead to improved process modelling through direct validation and allow for property optimization through direct microstructure control.

304 stainless steel↗
DOE OSTI2023

Sarcocystis cruzi (Hasselmann, 1923) Wenyon, 1926: redescription, molecular characterization and deposition of life cycle stages specimens in the Smithsonian Museum

Currently, 7 named Sarcocystis species infect cattle: Sarcocystis hirsuta, S. cruzi, S. hominis, S. bovifelis, S. heydorni, S. bovini and S. rommeli; other, unnamed species also infect cattle. Of these parasites of cattle, a complete life cycle description is known only for S. cruzi, the most pathogenic species in cattle. The life cycle of S. cruzi was completed experimentally in 1982, before related parasite species were structurally characterized, and before the advent of molecular diagnostics; to our knowledge, no archived frozen tissues from the cattle employed in the original descriptions remain for DNA characterization. Here, we isolated DNA from a paraffin-embedded kidney of a calf experimentally infected with S. cruzi in 1980; we then sequenced portions of 18S rRNA, 28S rRNA, COX1 and Acetyl CoA genes and verified that each shares 99–100% similarity to other available isolates attributed to S. cruzi from naturally infected cattle. We also reevaluated histological sections of tissues of calves experimentally infected with S. cruzi in the original description, exploiting improvements in photographic technology to render clearer morphological detail. Finally, we reviewed all available studies of the life cycle of S. cruzi, noting that S. cruzi was transmitted between bison (Bison bison) and cattle (Bos taurus) and that the strain of parasite derived from bison appeared more pathogenic than the cattle strain. Based on these newfound molecular, morphological and physiological data, we thereby redescribed S. cruzi and deposited reference material in the Smithsonian Museum for posterity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

An integrated in vivo/in vitro framework to enhance cell-free biosynthesis with metabolically rewired yeast extracts

Cell-free systems using crude cell extracts present appealing opportunities for designing biosynthetic pathways and enabling sustainable chemical synthesis. However, the lack of tools to effectively manipulate the underlying host metabolism in vitro limits the potential of these systems. Here, we create an integrated framework to address this gap that leverages cell extracts from host strains genetically rewired by multiplexed CRISPR-dCas9 modulation and other metabolic engineering techniques. As a model, we explore conversion of glucose to 2,3-butanediol in extracts from flux-enhanced Saccharomyces cerevisiae strains. We show that cellular flux rewiring in several strains of S. cerevisiae combined with systematic optimization of the cell-free reaction environment significantly increases 2,3-butanediol titers and volumetric productivities, reaching productivities greater than 0.9 g/L-h. We then show the generalizability of the framework by improving cell-free itaconic acid and glycerol biosynthesis. Our coupled in vivo/in vitro metabolic engineering approach opens opportunities for synthetic biology prototyping efforts and cell-free biomanufacturing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Data from Enhanced 2′-Fucosyllactose Production by Engineered Saccharomyces cerevisiae using Xylose as a Co-Substrate

2′-Fucosyllactose (2′-FL), a human milk oligosaccharide with confirmed benefits for infant health, is a promising infant formula ingredient. Although Escherichia coli , Saccharomyces cerevisiae , Corynebacterium glutamicum , and Bacillus subtilis have been engineered to produce 2′-FL, their titers and productivities need be improved for economic production. Glucose along with lactose have been used as substrates for producing 2′-FL, but accumulation of by-products due to overflow metabolism of glucose hampered efficient production of 2′-FL regardless of a host strain. To circumvent this problem, we used xylose, which is the second most abundant sugar in plant cell wall hydrolysates and is metabolized through oxidative metabolism, for the production of 2′-FL by engineered yeast. Specifically, we modified an engineered S. cerevisiae strain capable of assimilating xylose to produce 2′-FL from a mixture of xylose and lactose. First, a lactose transporter (Lac12) from Kluyveromyces lactis was introduced. Second, a heterologous 2′-FL biosynthetic pathway consisting of enzymes Gmd, WcaG, and WbgL from E. coli was introduced. Third, we adjusted expression levels of the heterologous genes to maximize 2′-FL production. The resulting engineered yeast produced 25.5 g/L of 2′-FL with a volumetric productivity of 0.35 g/L∙h in a fed-batch fermentation with lactose and xylose feeding to mitigate the glucose repression. Interestingly, the major location of produced 2′-FL by the engineered yeast can be changed using different culture media. While 72% of the produced 2′-FL was secreted when a complex medium was used, 82% of the produced 2′-FL remained inside the cells when a minimal medium was used. As yeast extract is already used as food and animal feed ingredients, 2′-FL enriched yeast extract can be produced cost-effectively using the 2′-FL-accumulating yeast cells.

Conversion↗
DOE OSTI2022

HFTS-2 (Final Report)

This report delves into the research program, identified tasks, various studies, observations, results, and conclusions under the Hydraulic Fracturing Test Site (HFTS-2) project. This test site is located in Loving County close to the Texas, New Mexico border. The program targeted the Wolfcamp formation in Delaware Basin. The aim of the project was to improve our understanding of hydraulic fracturing processes to not only optimize unconventional resource development in US Basins but to minimize environmental footprint as well. Various new diagnostic technologies were demonstrated at this site, including distributed acoustic microseismic, high resolution strain using Rayleigh frequency band (DSS-RFS), and in-fill proppant logging tool. Significant conclusions from this study include: 1) lateral and vertical fracture growth mapping as well as proppant transport behavior, 2) Use of DSS-RFS as a diagnostic tool to understand cluster level behavior, 3) Validation of proppant log, both at core scale as well as in-fill well implementation, and 4) New modeling tools to map far-field strain response using distributed strain sensing data. Specifically, far-field fracture distribution is influenced by linear fracture corridors defined by the stress-state as well as clustering behavior influenced by spatio-temporal effects. Depletion impacts on new stimulation was demonstrated and technically quantified. Significant vertical fracture height growth was observed. However, our understanding is limited by available gauge data availability. Numerical strain modeling techniques have been developed and demonstrated to help understand observed strain response behavior. Finally, proppant log has been further validated as a useful tool to map propped zones within the SRV. It has also shown very strong correlation with observed drawdown behavior at this test site. This report will detail many of these studies as well as technical results and conclusions from said studies. These include general subsurface characterization work, completion designs as implemented, studies looking at fracture geometry, high resolution microseismic study including source mechanisms, advanced DSS-RFS studies including drainage characterization, core characterization results, proppant analysis (core and in-fill child well), geochemistry, etc.

02 PETROLEUM↗
DOE OSTI2023

2.3.2.100 - Biological Lignin Valorization (BLV)

The Biological Lignin Valorization (BLV) project develops microbial strains and associated bioprocesses to convert lignin-derived aromatic compounds into value-added bioproducts. Our main objective in the BLV project is to achieve industrially relevant bioproduction metrics that can directly contribute to the economic viability and improved sustainability of the integrated lignocellulosic biorefinery, in collaboration with complementary BETO-funded lignin valorization projects. Specifically, the BLV project works closely with the BETO-funded Lignin Utilization project, which provides bio-available aromatic compounds from chemo-catalytic lignin depolymerization. We use the robust soil bacterium, Pseudomonas putida, as our primary microbial host for the conversion of lignin-derived compounds to bioproducts. To date, we have focused on atom-efficient bioproducts that can be used as either direct replacement chemicals or performance-advantaged bioproducts, including cis,cis-muconic acid, beta-ketoadipic acid, and 2-pyrone-4,6-dicarboxylic acid. From model aromatic substrates, we have achieved titers of each of these compounds approaching 40 g/L and productivity values ranging from 0.5 to over 1 g/L/hr, all at 90% molar yield or higher. From real lignin streams, we have thus far achieved 24 g/L, 0.66 g/L/hr, and theoretical yield of beta-ketoadipic acid. A major pursuit now is to reach industrially relevant performance metrics on an expanded slate of lignin-derived streams.

BIOMASS FUELS↗
DOE OSTI2020

A matrix-free approach for finite-strain hyperelastic problems using geometric multigrid

This paper investigates matrix-free algorithms for problems in quasi-static finite-strain hyperelasticity. Iterative solvers with matrix-free operator evaluation have emerged as an attractive alternative to sparse matrices in the fluid dynamics and wave propagation communities because they significantly reduce the memory traffic, the limiting factor in classical finite element solvers. Specifically, we study different matrix-free realizations of the finite element tangent operator and determine whether generalized methods of incorporating complex constitutive behavior might be feasible. Furthermore, in order to improve the convergence behavior of iterative solvers, we also propose a method by which to construct level tangent operators and employ them to define a geometric multigrid preconditioner. Additionally, the performance of the matrix-free operator and the geometric multigrid preconditioner is compared to the matrix-based implementation with an algebraic multigrid (AMG) preconditioner on a single node for a representative numerical example of a heterogeneous hyperelastic material in two and three dimensions. We find that matrix-free methods for finite-strain solid mechanics are very promising, outperforming linear matrix-based schemes by two to five times, and that it is possible to develop numerically efficient implementations that are independent of the hyperelastic constitutive law.

42 ENGINEERING↗
DOE OSTI2021

Fabrication of Six Degrees-of-Freedom Hexflex Positioner With Integrated Strain Sensing Using Nonlithographically Based Microfabrication

In this study, a process flow is described for the low cost, flexible fabrication of metal micro-electromechanical systems (MEMS) with high performance integrated sensing. The process is capable of producing new designs in ≈1 week at an average unit cost of <$1 k/device even at batch sizes of ≈1–10, with expected sensing performance limits of about 135 dB over a 10 kHz sensor bandwidth. This is a ≈20× reduction in cost, ≈25× reduction in time, and potentially >30× increase in sensing dynamic range over comparable state-of-the-art compliant nanopositioners. The nonlithographically based microfabrication (NLBM) process is uniquely suited to create high performance nanopositioning architectures which are customizable to the positioning requirements of a range of nanoscale applications. These can significantly reduce the cost of nanomanufacturing research and development, as well as accelerate the development of new processes and the testing of fabrication process chains without excess capital investment. A six degrees-of-freedom (6DOF) flexural nanopositioner with integrated sensing for all 6DOF was fabricated using the newly developed process chain. The fabrication process was measured to have ≈30 μ m alignment. Sensor arm, flexure, and trace widths of 150 μ m, 150 μ m, and 800 μ m, respectively, were demonstrated. Process capabilities suggest lower bounds of 25 μ m, 50 μ m, and 100 μ m, respectively. Dynamic range sensing of 52 dB was demonstrated for the nanopositioner over a 10 kHz sensor bandwidth. Improvements are proposed to approach sensor performance of about 135 dB over a 10 kHz sensor bandwidth.

42 ENGINEERING↗
DOE OSTI2025

Turbulent burning velocity of lean premixed hydrogen/air flames at engine conditions: Effects of turbulence intensity and length scale

For turbulent lean premixed hydrogen flames with strong thermodiffusively instabilities, most previous studies have focused on the influence of turbulence intensity, whereas the role of turbulence length scale is less well understood. Here, this study addresses this gap by conducting direct numerical simulations (DNS) of statistically planar turbulent premixed flames for a lean (ϕ=0.35) hydrogen/air mixture under independently varied turbulence intensity (u') and length scale (l T ) at engine-relevant thermodynamics conditions. Results show that as u' increases, the flame front becomes increasingly wrinkled, forming smaller cellular structures. In contrast, l T variations do not significantly alter the size of these structures. For the turbulent burning velocity (S T ), the normalized S T (i.e., S T /S L , where S L is the laminar flame speed) increases linearly with u', driven by both enhanced flame surface wrinkling (i.e., increased A T /A L ) and enhanced local burning rate (i.e., increased I 0 ). However, increasing l T reduces I 0 , despite a continued increase in A T /A L , resulting in only a marginal increase in S T /S L . To reveal the underlying mechanisms, especially the decreasing trend of I 0 with l T , local flame dynamics analyses are performed. It is found that as l T increases, the interaction between thermodiffusive effects and turbulence weakens due to the reduced tangential strain rate, while the flame curvature remains largely unchanged. This suppresses local reactivity enhancement and thus decreases I 0 , In contrast, an increase in u' enhances the interaction by amplifying both curvature fluctuation and tangential strain rate, leading to increased local reactivity (increased I 0 ). Finally, based on the DNS data, several new scaling models are proposed for the three global properties, S T /S L , A T /A L , and I 0 , and showed improvements compared to existing models. These findings provide new insights into the flame-turbulence interactions in thermodiffusively unstable hydrogen flames. The DNS dataset is also useful for the development of turbulent combustion models applicable to practical engine simulations.

Engine-relevant condition↗
DOE OSTI2023

Strengthening mechanisms, hardening/softening behavior, and microstructure evolution in an LPSO magnesium alloy at elevated temperatures

Here, rapid degradation of the mechanical properties of conventional Mg alloys with temperature precludes their wide application in industry. The LPSO (long period stacking ordered) Mg alloys, on the other hand, show considerable potential to achieve excellent high-temperature mechanical performance. In this study, a Mg-5.1Y-2.4Zn (wt.%) extrusion alloy with the microstructure comprising of α-Mg matrix and LPSO phase was prepared. It is shown that the yield strength of the alloy at 200 °C retained ~83% of the yield strength of 198 MPa at room temperature (RT). Importantly, the ductility also improved, owing to the increased non-basal slip activities at elevated temperatures. In contrast to RT and 200 °C, the alloy exhibited softening tensile behavior with an apparent loss of yield strength at 300 °C. In-situ lattice strain analysis revealed that load transfer from α-Mg to LPSO remains effective at temperatures up to 200 °C, governing the high yield strength of the alloy. The post-mortem analysis by means of electron microscopy confirmed that the LPSO phase is structurally stable at 200 °C. In particular, the high strain hardenability is rationalized by the sandwiched LPSO structures together with stacking faults serving as effective obstacles to the motion of non-basal dislocations. The load transfer effect disappears at the temperature of 300 °C, resulting in the fast deterioration of strength of the alloy. The cracking of the LPSO phase along with the recrystallizing of α-Mg grains were found to be the main causes for the softening behavior of the alloy at 300 °C.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Triggering the stringent response enhances synthetic methanol utilization in Escherichia coli

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, i.e. the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here in this paper, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. By activating the stringent/stress response via ppGpp overproduction, or DksA and RpoS overexpression, we demonstrate improved biosynthesis of proteinogenic amino acids via endogenous upregulation of amino acid synthesis pathway genes. Thus, we were able to achieve biosynthesis of several limiting amino acids from methanol-derived carbon, in contrast to the control methylotrophic E. coli strain. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via stringent/stress response activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Enhanced 2'-Fucosyllactose production by engineered Saccharomyces cerevisiae using xylose as a co-substrate

2'-Fucosyllactose (2'-FL), a human milk oligosaccharide with confirmed benefits for infant health, is a promising infant formula ingredient. Although Escherichia coli, Saccharomyces cerevisiae, Corynebacterium glutamicum, and Bacillus subtilis have been engineered to produce 2'-FL, their titers and productivities need be improved for economic production. Glucose along with lactose have been used as substrates for producing 2'-FL, but accu- mulation of by-products due to overflow metabolism of glucose hampered efficient production of 2' -FL regardless of a host strain. To circumvent this problem, we used xylose, which is the second most abundant sugar in plant cell wall hydrolysates and is metabolized through oxidative metabolism, for the production of 2'-FL by engi- neered yeast. Specifically, we modified an engineered S. cerevisiae strain capable of assimilating xylose to pro- duce 2' -FL from a mixture of xylose and lactose. First, a lactose transporter (Lac12) from Kluyveromyces lactis was introduced. Second, a heterologous 2'-FL biosynthetic pathway consisting of enzymes Gmd, WcaG, and WbgL from Escherichia coli was introduced. Third, we adjusted expression levels of the heterologous genes to maximize 2'-FL production. The resulting engineered yeast produced 25.5 g/L of 2'-FL with a volumetric productivity of 0.35 g/L∙h in a fed-batch fermentation with lactose and xylose feeding to mitigate the glucose repression. Interestingly, the major location of produced 2'-FL by the engineered yeast can be changed using different culture media. While 72% of the produced 2'-FL was secreted when a complex medium was used, 82% of the produced 2'-FL remained inside the cells when a minimal medium was used. In conclusion, as yeast extract is already used as food and animal feed ingredients, 2'-FL enriched yeast extract can be produced cost-effectively using the 2'-FL-accumu- lating yeast cells.

2′ -fucosyllactose↗
DOE OSTI2024

Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry–based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC 50 cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets.

Science & Technology - Other Topics↗