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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
DOE OSTI2024

Electrically Insulated Catalyst–Ionomer Anode Interfaces toward Durable Alkaline Membrane Electrolyzers

Anion-exchange-membrane water electrolysis (AEMWE) is an emerging technology for scalable hydrogen production. AEMWE has poor durability when operating without supporting electrolyte due to the oxidation of ionomers and membranes in contact with the anode oxygen evolution reaction (OER) catalyst. We report a new “passivated” anode architecture for AEMWE where the OER catalysts and ionomers are physically separated with a thin film amorphous oxide coating that is electrically insulating but conductive to hydroxide ions. We find that 2–3 nm of HfO x passivation layers show sufficient hydroxide ion transport to minimally limit the cell performance while suppressing ionomer degradation with both Ir (500 mA·cm –2 for 40 h) and CoO x (1.0 A·cm –2 for 100 h) model porous-transport-layer-supported catalysts in AEMWE. As a result, this interfacial engineering approach guides electrode design to improve the durability of AEMWE, particularly for systems operating with pure-water feed.

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

Ternary SiGeSn alloy nanocrystals via nonthermal plasma synthesis

We report on the synthesis of ternary SiGeSn nanocrystals (NCs) produced via nonthermal plasma synthesis from silane (SiH 4 ), germane (GeH 4 ), and tetramethylstannane (Sn(CH 3 ) 4 ) precursor sources. Detailed structural, chemical, and vibrational analyses show that all three elements are incorporated both on the NC surface and within the NC core. Incorporation of Sn into the NC core is realized using a secondary injection of SiH 4 and GeH 4 precursor gases in the after-glow region of the plasma, which kinetically traps Sn in the core. We demonstrate compositional tunability of the SiGeSn NCs in which the Si and Ge ratios can be varied broadly at low Sn concentrations. We also show tunability of the Sn content up to ~2 atomic percent as revealed by ICP-MS analysis. More generally, this report demonstrates how nonthermal plasma synthesis can be used to produce metastable ternary nanostructured alloys involving thermodynamically insoluble constituents.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2020

Joint Genome Institute Analysis Workflow Service (JAWS) v2.7

The U.S. Department of Energy Joint Genome Institute (JGI) has developed the JGI Analysis Workflow Service (JAWS) as a distributed framework to run computational workflows across diverse high-performance computing (HPC) and cloud environments. JAWS enhances the reusability, scalability, and robustness of scientific workflows by orchestrating data movement, code execution, and results retrieval across multiple DOE facilities. At its core, JAWS integrates the Cromwell workflow engine to run workflows expressed in the Workflow Description Language (WDL), ensuring portability and interoperability. To provide consistent runtime environments, JAWS employs container technologies such as Shifter, Apptainer, and Docker. Workflow tasks are managed via HTCondor on HPC backends, while Globus ensures secure and efficient data transfer between sites. JAWS is deployed as a multi-site workflow manager across national laboratory computing facilities, with dedicated instances supporting community projects such as the National Microbiome Data Collaborative (NMDC) and KBase. This distributed, service-oriented architecture enables users to "write once, run anywhere," providing scalable, production-quality workflow execution.

Kirton, Edward↗
DOE OSTI2026

Photo-Reactive Amine-Based Direct Air Capture and Conversion of CO2

This study presents a novel photochemical approach to direct air capture (DAC) and CO2 conversion, utilizing a ruthenium-modified mesoporous TiO2 composite infused with linear polyethyleneimine (L-PEI) and enhanced by light absorbing and earth abundant titanium nitride (TiN). This light-activated system operates at ambient pressure and addresses long-standing challenges in conventional amine-based thermal reactive carbon capture (RCC), including amine degradation and CO2 slip. Our findings demonstrate that L-PEI effectively stabilizes CO2 adsorption and facilitates high-yield methanation over 50 cycles with a non-flammable forming gas mixture (approximately 5% H2). Comparatively, composites incorporating small-molecule amines exhibited poor stability under illumination, while highly mobilie branched PEI (B-PEI) formulations suffered from significant catalyst deactivation. A technoeconomic analysis suggests that methane synthesis via this platform could be achieved at costs below $5/kg under current electrocatalytic hydrogen pricing. These findings highlight the potential of this approach to enhance energy security by enabling decentralized, scalable fuel production from atmospheric CO2.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Scalable Membrane Electrode Assembly Stack Production for Reliable Thermal Electrochemical Converters (SMART)

This Final Close Out Report documents all activities, progress, and results accomplished under the SMART project, funded by the Department of Energy (DOE), during Budget Period 1 (BP1), covering 10/01/2023 to 07/31/2025. Although official preaward approval was granted on 05/10/2024, contracting delays shifted the award and formal project start to 10/01/2024. In the absence of an official kick-off meeting, early interactions focused on planning for key technical challenges, particularly the design and logistics for the JTEC device test platform.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2020

Scalable Electrolytic Systems for Renewable Hydrogen Production (Cooperative Research and Development Final Report, CRADA Number CRD-18-747)

The project focuses on offshore wind energy which is an emergent renewable energy source in the United States. Onsite hydrogen production for this sector is not available. The overall goal of GTA's work is development of scalable multi-megawatt water electrolysis systems that exclude platinum group metals, are constructed from readily available commodity materials and are mass produced using advanced manufacturing and robotics. They fabricated and successfully tested a scalable TRL 4 laboratory prototype that demonstrated promising results for achieving the goal. They further performed calculations and prepared scale drawings for an envisioned onsite TRL 8 electrolytic hydrogen production system at an offshore 8 MW wind turbine. The work plan of the CRADA proposal between NREL and GTA focuses on validation of the current TRL 4 prototype with potential development and refinement for advancement to a TRL 5 system. GTA, Inc. proposes joining the H2@Scale consortium to leverage DOE funds, benefit from and contribute to the common knowledge-base and work with NREL as a CRADA partner.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2021

Roll-to-Roll Advanced Materials Manufacturing DOE Laboratory Collaboration (FY2020 Final Report)

R2R processing is used to manufacture a wide range of products for various applications which span many industrial business sectors. The overall R2R methodology has been in use for decades and this continuous technique traditionally involves deposition of material(s) onto moving webs, carriers or other continuous belt-fed or conveyor-based processes that enable successive steps to build a final version which serves to support the deposited materials. Established methods that typify R2R processing include tape casting, silk-screen printing, reel-to-reel vacuum deposition/coating, and R2R lithography. Products supported by R2R manufacturing include micro-electronics, electro-chromic window films, PVs, fuel cells for energy conversion, battery electrodes for energy storage, and barrier and membrane materials. Due to innovation in materials and process equipment, high-quality yet very low-cost multilayer technologies have the potential to be manufactured on a very cost-competitive basis. To move energy-related products from high-cost niche applications to the commercial sector, the means must be available to enable manufacture of these products in a cost-competitive manner that is affordable. Fortunately, products such as fuel cells, thin- and mid-film PVs, batteries, electrochromic and piezoelectric films, water separation membranes, and other energy saving technologies readily lend themselves to manufacture using R2R approaches. However, more early-stage research is needed to solve the challenge of linking the materials (particles, polymers, solvents, additives) used in ink and slurry formulations and the coating and drying processes to the ultimate performance of the final R2R product, especially for a process that uses multiple layers of deposition to achieve the end product. To solve the problems associated with these challenges, the R2R Collaboration is executing a research program with outcomes that will ultimately link modeling, processing, metrology and defect detection tools, thereby directly relating the properties of constituent particles and processing conditions to the performance of final devices. This collaborative approach was designed to foster identification and development of materials and processes related to R2R for clean-energy materials development. Using computational and experimental capabilities by acknowledged subject matter experts within the supported National Laboratory system, this project leverages the capabilities and expertise at each of five National Laboratories to further the development of multilayer technologies that will enable high-volume, cost-competitive platforms. A typical R2R process has three steps: (1) mixing of particles and various constituents in a slurry, (2) coating of the ink/slurry mixture on a substrate, and (3) drying/curing and processing of the coating. Final performance of devices made via R2R processes is dependent on the active materials (e.g., electrochemical particles in battery or fuel cell electrodes) and the device structure that stems from the governing component interactions within the various steps. However, a fundamental understanding of the underlying mechanisms and phenomena is still lacking, which is why industrial-scale R2R process development and manufacturing is still largely empirical in nature. The FY 2019 through FY 2021 program addresses aspects of the following two targets from the AMO Multi-Year Program Plan: (1) Target 8.1 Develop technologies to reduce the cost per manufactured throughput of continuous R2R manufacturing processes. (A) Increasing throughput of R2R processes by 5 times for batteries (to 50 square feet per minute (50 ft 2 /min)) and capacitors and 10 times for printed electronics and the manufacture of other substrates and MEs used in support of these products. (B) Developing resolution capabilities to enable registration and alignment that will detect, align, and co-deposit multiple layers of coatings and print < 1-micron (1 µm) features using continuous process scalable for commercial production. (C) Developing scalable and reliable R2R processes for solution deposition of ultra-thin (<10 nm) films for active and passive materials. (D) Develop in-line multilayer coating technology on thin films with yields greater than 95%. (2) Target 8.2 Develop in-line instrumentation tools that will evaluate the quality of single and multilayer materials in-process. (A) Developing in-line QC technologies and methodologies for real-time identification of defects and expected product properties “in-use/application” during continuous processing at all size-scales with a focus on the “micro” and “nano” scale traces, lines, and devices, i.e., <1 μm at 300 ft./min for R2R processing in air and <10 nm at 20 ft./min for vacuum (B) Developing technologies to increase the measurement frequency of surface rheology without significant cost increases with a goal of a 10-nanometer in-line profilometry at a production rate of 100,000 square millimeters per minute (100,000 mm 2 /min).

42 ENGINEERING↗
DOE OSTI2025

Levelized cost and carbon intensity of solar hydrogen production via water splitting using a scalable and intrinsically safe photocatalytic Z-scheme raceway system

Generating hydrogen from local energy resources such as solar or wind would unlock a low-carbon energy carrier that could be used to reduce greenhouse gas emissions in sectors such as industry and transportation. Yet, the allocation of new or existing power generation solely to hydrogen production remains contentious due to disputes regarding emissions accounting. Photocatalytic (PC) hydrogen production technologies offer a unique solution, as hydrogen is produced directly from solar energy and water, without the need for electricity generation. However, cost projections for all photocatalytic designs to date have suggested that they are not cost competitive compared to conventional electrolysis systems manufactured at scale. Herein, we offer the first illustrative benchmark of cost and carbon intensity of hydrogen produced in a type 2 “Z-scheme” photocatalytic reactor design, which employs suspended semiconducting nanoconductor particles organized into two stacked volumes in a raceway design. The “Z-scheme” system utilizes two separate photoabsorber particles, tuned to drive either the hydrogen evolution reaction or the oxygen evolution reaction individually, connected via a reversible, charge transfer redox couple in solution. Furthermore, the results suggest a highly competitive and scalable technology, that justifies further experimental validation and prototyping in the field.

Carbon↗
DOE OSTI2024

Epitaxial heterointerfacial electron bridge synchronizes oxygen evolution activity and stability on a layered double hydroxide surface

Scalable green hydrogen production via electrocatalytic water splitting is largely restricted by the insufficient activity and stability of oxygen evolution reaction (OER) catalysts at the anode. As a class of the most active OER catalysts in alkaline electrolyzers, the application of layered double hydroxides (LDHs) remains a main challenge owing to the unstable lattice oxygen dissolution due to the dominant lattice oxygen-involving OER mechanism during long-term operation. Herein, we found that using an epitaxial hetero-interfacing nickel hydroxide (namely Ni(OH) 2 ) as an electron bridge between an active FeCo LDH and Ni foam support to form an LDH*/NFO catalyst, the electronic storage capacity around the Fermi level (-0.5 to +0.5 eV, e-D FE ) sharply increases from 0.93 per cell to 1.51 per cell. Subsequently, we demonstrate that this high e-D FE enables ceaseless and fast power injection into the kinetic process of intermediate species conversion and inhibits lattice oxygen dissolution in the active FeCo LDH. Consequently, it demonstrated a low OER overpotential of 246 mV at a current density of 100 mA cm -2 and ultrahigh stability for up to 3500 hours with an ultraslow overpotential increase rate of 9.4 × 10 -3 mV h -1 . Therefore, we developed an epitaxial hetero-interfacial electron bridging strategy to synchronize the activity and stability of available catalysts for scalable green hydrogen production via electrocatalytic water splitting.

25 ENERGY STORAGE↗
DOE OSTI2020

Electrochemical CO 2 Utilization: Scalable System Operation for Formic Acid Production

In recent years, research into the electrochemical reduction of CO 2 has grown exponentially. Formic acid (FA) has become a particular value product from CO 2 due to its versatility [1], optimal atom economy [2], and thermodynamic favorable [3]. FA can be produced electrochemically via a direct two-electron transfer process involving CO 2 with a proton source, requiring less energy input and fewer reaction steps than the conventional Kemira process. However, product selectivity, electrode stability, and low faradic efficiency due to increased resistance under constant current, remain key issues for CO 2 reduction to FA [4]. University of Kentucky’s Center for Applied Energy Research (UK CAER) is currently investigating reactor designs to address the challenges associated with electrochemical CO 2 conversion to FA [5]. The current reactor system employs: (1) an organic-based charge carrier which shuttles charge directly to the catalyst to enable CO 2 reduction to FA; (2) novel electrode materials to mitigate large voltages and improve conductivity; and (3) a flow system which not only allows for the volumetric scale-up of both charge carrier and catalyst, but also decouples the charger carrier re-energized and FA production processes to protect the catalyst’s stability due to overpotential. Through careful adjustment of electrode, charge carrier, and electrolyte selection, cell resistances have decreased by over 15%, facilitating conduction necessary for effective CO 2 reduction to FA. The system uses a highly specific engineered catalyst, which has produced over 100 mM FA at a rate of over 10 mM FA/hour following the aforementioned electrode/charge carrier changes. System design considerations (flow rate, bulk volume) and modeling of the system will also be discussed.

20 FOSSIL-FUELED POWER PLANTS↗
DOE OSTI2024

Co-synthesis of Hydrogen and High-Value Carbon Products from Methane Pyrolysis

The ARPA-E Methane Pyrolysis Project successfully developed a scalable technology for hydrogen production with low-CO x emission through methane pyrolysis, co-producing high-value carbon nanotubes (CNTs). The project focused on optimizing reactor design, enhancing catalyst performance, and assessing techno-economic feasibility to create a commercially viable and environmentally sustainable process. The fluidized bed reactor achieved over 90% methane (CH 4 ) conversion by using a 5% CO 2 co-feed, which stabilizes carbon yields and minimizes catalyst deactivation. This setup allowed for continuous operation across ten cycles, each consisting of a 14-minute pyrolysis phase followed by a 10-minute dislodging phase to remove a fraction of the accumulated carbon, resulting in stable performance and high-quality CNT production. In parallel, monolith reactors coated with Fe demonstrated a sustained methane conversion of 73% while producing CNTs with high crystallinity. Although promising for continuous operation, monolith reactors face challenges in coating durability and scalability, highlighting areas for further optimization in commercial applications. Catalyst formulation played a key role in enhancing process efficiency. The core catalyst used was 5%Fe/Al 2 O 3 (wt%), optimized through wet impregnation, which improved CNT morphology, yielding longer and more uniform CNTs. The catalyst's performance was further enhanced by adding promoters: 2.5 wt% Ni increased methane conversion close to the thermodynamic limit, while 2.5 wt% Mn improved CNT alignment and crystallinity, and 1.5 wt% NaCl boosted CNT morphology but slightly lowered methane conversion. These adjustments allowed the reactor to maintain high methane conversion while producing high-quality CNTs, enabling stable performance over multiple cycles. To address carbon buildup and ensure uninterrupted operation, a pneumatic conveying tube was implemented for effective carbon dislodging in the fluidized bed configuration. CO 2 and H 2 O co-feeds were also introduced to enhance carbon removal, with CO 2 boosting CNT yield by approximately 15%. This setup enabled stable reactor operation across multiple cycles, preventing clogging and minimizing catalyst wear, making the process suitable for industrial scaling. Techno-economic analysis (TEA) projected hydrogen production costs between $\$$1.00 and $\$$1.64 per kilogram, with CNT values assumed at $\$$375/ton and $\$$100/ton. The life cycle assessment showed that CO 2 emissions could be as low as 0.64 kg CO 2 e/kg H 2 at 95% methane conversion assuming an electricity input of 50 kg CO 2 e/MWh. Even at 50% methane conversion, emissions remained below 1 kg CO 2 e/kg H 2 , demonstrating the process's low-emission potential and making it a viable alternative to traditional steam methane reforming. Overall, the results from this project demonstrate the feasibility of a pyrolysis process where carbon is continuously removed from the catalyst surface and hydrogen is continuously produced until a catalyst regeneration step is required to fully clean the catalyst surface and renew catalyst performance. Major open challenges are related to avoiding the loss of catalyst material in the dislodged carbon during fluidized bed conditions, since our best result demonstrated a carbon purity of ~70 wt. % (rest being iron and alumina). A monolith reactor was used to favor dislodgement of carbon compared to fluidized bed conditions but our results do not demonstrate an advantage of the monolith configuration. Catalyst performance was similar to fluidized bed conditions with slower deactivation rates overall, but we could not observe carbon dislodging in any of the tens of experiments that were run at Stanford. Our results show that the most relevant areas of improvement are related to the fundamental understanding of the iron-carbon interface for dislodging, and the development of catalyst that can produce CNTs via a base-growth mechanism such that catalyst is not lost in the dislodgement steps. The final report documents all findings and methodologies in detail, providing a valuable resource for the scientific community. By building on these results, researchers can further advance methane pyrolysis technology, moving toward a more sustainable, scalable pathway for hydrogen production. This work lays the foundation for future research and commercial efforts to reduce emissions in hydrogen production while generating valuable carbon products.

08 HYDROGEN↗
DOE OSTI2020

Flexible polyurethanes, renewable fuels, and flavorings from a microalgae oil waste stream

Renewable polymers have become an important focus in next-generation materials, and algae biomass offers an environmentally low-impact feedstock that can serve multiple uses. This study aims to develop a scalable methodology for production of microalgae-based polyols for polyurethane synthesis from waste oils derived from algae biomass. Following separation of omega-3 fatty acids from algae oil, residual oils can offer valuable building blocks for petrochemical replacements. However, unlike vegetable oils, algae oils contain organic contaminants, including photosynthetic pigments and hydrophobic cofactors that can complicate preparative methodologies. Here we convert and purify waste streams from omega-3 depleted Nannochloropsis salina algae oil, with major components consisting of palmitic and palmitoleic acid, into azelaic acid (AA) as a building block for flexible polyurethanes, with a simultaneous production of heptanoic acid (HA) as a flavor and fragrance precursor. Conversion of free fatty acid mixtures into a soft soap allows extraction of organic contaminants, and urea complexation provides isolated palmitoleic acid, which is subsequently ozonolyzed to produce AA and HA. Bio-based polyester diols are prepared from AA via esterification to provide a polyol monomer for flexible polyurethane foam preparation. The HA co-product is modified to produce the flavoring agent methyl heptanoate and also decarboxylated to produce hexane as a renewable solvent. This scalable process can be performed on oils from multiple algal species, offering valuable monomers from a highly sustainable source.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Methane Pyrolysis for CO2-free H2 and Carbon Nanomaterials (Abstract)

We propose to continue to develop a new process for producing CO2-free hydrogen (H2) from inexpensive and domestically-abundant natural gas (NG), while simultaneously reducing H2’s net production cost to $1.0/kg through the sale of valuable crystalline solid carbon co-product. Producing clean hydrogen at this price is a DOE Hydrogen Energy Earthshot goal. Cost effective production of clean H2 is also of commercial relevance to project partners Southern California Gas Company (SoCalGas) and startup company C4-MCP, who aim to further develop, demonstrate at scale, and ultimately deploy the new process technology developed on this project in order to meet regulatory demands in the State of California. In the current project we have focused on i) understanding the catalyst science for thermocatalytic decomposition of methane (TCD), which resulted in the development of a patent pending bimetallic catalyst offering favorable activity, stability, and selectivity under industrially relevant process conditions, ii) developing a novel, patent pending process to enable the separation of produced carbon and catalyst, and re-synthesis of the catalyst using recycled materials, iii) performing limited characterization of the produced carbon materials, and iv) performing detailed process modeling in order to perform techno economic assessment. The additional scope proposed here will accelerate the commercial deployment of TCD for CO2-free H2 and valuable solid carbon nanotubes (CNT) co-product, by i) scaling up the production of CNT co-product using a scalable, fluidized bed reactor (25 g catalyst scale versus the 1 g catalyst scale demonstrated to-date), ii) producing at least 40 g of CNT product, produced via multiple cycles of TCD, carbon-catalyst separation, and catalyst re-synthesis, to enable the production of sufficient quantities of solid carbon so as to explore its market potential, iii) understanding the quality of the co-product CNTs, produced at larger scale, through advanced characterization, and iv) beginning to explore multiple promising high volume carbon product applications (thermoplastics, automotive composites, battery, and cement reinforcement applications).

08 HYDROGEN↗
DOE OSTI2024

Toward Mass-Production of Transition Metal Dichalcogenide Solar Cells: Scalable Growth of Photovoltaic-Grade Multilayer WSe2 by Tungsten Selenization

Semiconducting transition metal dichalcogenides (TMDs) are promising for high-specific-power photovoltaics due to their desirable band gaps, high absorption coefficients, and ideally dangling-bond-free surfaces. Despite their potential, the majority of TMD solar cells to date are fabricated in a nonscalable fashion, with exfoliated materials, due to the lack of high-quality, large-area, multilayer TMDs. Here, we present the scalable, thickness-tunable synthesis of multilayer WSe2 films by selenizing prepatterned tungsten with either solid-source selenium at 900 degrees C or H2Se precursors at 650 degrees C. Both methods yield photovoltaic-grade, wafer-scale WSe2 films with a layered van der Waals structure and superior characteristics, including charge carrier lifetimes up to 144 ns, over 14x higher than those of any other large-area TMD films previously demonstrated. Simulations show that such carrier lifetimes correspond to ~22% power conversion efficiency and ~64 W g-1 specific power in a packaged solar cell, or ~3 W g-1 in a fully packaged solar module. The results of this study could facilitate the mass production of high-efficiency multilayer WSe2 solar cells at low cost.

carrier lifetime↗
DOE OSTI2021

Scalable Polymeric Few-Nanometer Organosilica Membranes with Hydrothermal Stability for Selective Hydrogen Separation

Nanoporous silica membranes exhibit excellent H 2 /CO 2 separation properties for sustainable H 2 production and CO 2 capture but are prepared via complicated thermal processes above 400 °C, which prevent their scalable production at a low cost. Here, we demonstrate the rapid fabrication (within 2 min) of ultrathin silica-like membranes (~3 nm) via an oxygen plasma treatment of polydimethylsiloxane-based thin-film composite membranes at 20 °C. The resulting organosilica membranes unexpectedly exhibit H2 permeance of 280-930 GPU (1 GPU = 3.347 x 10 -10 mol m -2 s -1 Pa -1 ) and H2/CO2 selectivity of 93-32 at 200 °C, far surpassing state-of-the-art membranes and Robeson’s upper bound for H 2 /CO 2 separation. When challenged with a 3 d simulated syngas test containing water vapor at 200 °C and a 340 d stability test, the membrane shows durable separation performance and excellent hydrothermal stability. The robust H 2 /CO 2 separation properties coupled with excellent scalability demonstrate the great potential of these organosilica membranes for economic H 2 production with minimal carbon emissions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Chapter 21: Sustainable Technologies for Seaweed Conversion to Biofuels and Bioproducts

Seaweeds are attractive candidates to supply the future sustainable, photosynthetic, bioenergy feedstocks thanks to their cultivation promise in offshore marine farms, with year-round production, and no external nutrient requirements. Despite this potential, there are significant challenges associated with realizing both the cultivation and harvesting logistics, as well as in developing an efficient conversion platform to fuels and products. Effective and scalable and economically viable conversion processes tailored to a seaweed are discussed in detail and gaps on identified needs for yield and efficiency improvements. Among the conversion processes discussed here, anaerobic fermentation of seaweeds to bioenergy products, including organic acids and biomass, is promising to disrupt the current bioenergy landscape.

anaerobic digestion↗
DOE OSTI2024

Verazine biosynthesis from simple sugars in engineered Saccharomyces cerevisiae

Steroidal alkaloids are FDA-approved drugs (e.g., Zytiga) and promising drug candidates/leads (e.g., cyclopamine); yet many of the ≥697 known steroidal alkaloid natural products remain underutilized as drugs because it can be challenging to scale their biosynthesis in their producing organisms. Cyclopamine is a steroidal alkaloid produced by corn lily (Veratrum spp.) plants, and it is an inhibitor of the Hedgehog (Hh) signaling pathway. Therefore, cyclopamine is an important drug candidate/lead to treat human diseases that are associated with dysregulated Hh signaling, such as basal cell carcinoma and acute myeloid leukemia. Cyclopamine and its semi-synthetic derivatives have been studied in (pre)clinical trials as Hh inhibitor-based drugs. However, challenges in scaling the production of cyclopamine have slowed efforts to improve its efficacy and safety profile through (bio)synthetic derivatization, often limiting drug development to synthetic analogs of cyclopamine such as the FDA-approved drugs Odomzo, Daurismo, and Erivedge. If a platform for the scalable and sustainable production of cyclopamine were established, then its (bio)synthetic derivatization, clinical development, and, ultimately, widespread distribution could be accelerated. Ongoing efforts to achieve this goal include the biosynthesis of cyclopamine in Veratrum plant cell culture and the semi-/total chemical synthesis of cyclopamine. Herein, this work advances efforts towards a promising future approach: the biosynthesis of cyclopamine in engineered microorganisms. We completed the heterologous microbial production of verazine (biosynthetic precursor to cyclopamine) from simple sugars (i.e., glucose and galactose) in engineered Saccharomyces cerevisiae (S. cerevisiae) through the inducible upregulation of the native yeast mevalonate and lanosterol biosynthetic pathways, diversion of biosynthetic flux from ergosterol (i.e., native sterol in S. cerevisiae) to cholesterol (i.e., biosynthetic precursor to verazine), and expression of a refactored five-step verazine biosynthetic pathway. The engineered S. cerevisiae strain that produced verazine contains eight heterologous enzymes sourced from seven different species. Importantly, S. cerevisiae-produced verazine was indistinguishable via liquid chromatography-mass spectrometry from both a commercial standard (Veratrum spp. plant-produced) and Nicotiana benthamiana-produced verazine. To the best of our knowledge, this is the first report describing the heterologous production of a steroidal alkaloid in an engineered yeast. Verazine production was ultimately increased through design-build-test-learn cycles to a final titer of 83 ± 3 μg/L (4.1 ± 0.1 μg/g DCW). Finally, this research lays the groundwork for future microbial biosynthesis of cyclopamine, (bio)synthetic derivatives of cyclopamine, and other steroidal alkaloid natural products.

59 BASIC BIOLOGICAL SCIENCES↗