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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

An argument for using anaerobes as microbial cell factories to advance synthetic biology and biomanufacturing

Anaerobes thrive in the absence of oxygen and are an untapped reservoir of biotechnological potential. Therefore, bioprospecting efforts focused on anaerobic microbial diversity could rapidly uncover new enzymes, pathways, and chassis organisms to drive biotechnology innovation. Despite their potential utility, anaerobic fermenters are viewed as inefficient from a biochemical perspective because their metabolisms produce fewer ATP (~2) per molecule of glucose processed than heterotrophic respirers (~32–38 ATP). While aerobes excel at ATP generation, they are often less efficient than anaerobes at processes that compete with ATP generation for cellular resources. This perspective highlights how anaerobic adaptations are advantageous for synthetic biology and biomanufacturing applications through the engineering of microbial cell factories. We further highlight emerging applications of anaerobic bioprocessing, including the use of anaerobic metabolisms for lignocellulosic bioprocessing, human and environmental health, and value-added bioproduction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Cost impact of hexose-to-pentose sugar ratios for biomanufacturing

Central to the long-term vision for biomanufacturing is the ability to deconstruct plant cell walls to sugars that microbes can convert to products. Aside from glucose, the most abundant sugar in biomass is xylose, a pentose sugar. Industrially relevant microbes have been engineered to co-ferment xylose and glucose. Most nth plant technoeconomic analyses (TEAs) assume similar consumption rates and product yields for both sugars, but in reality, xylose is consumed more slowly. Feedstocks can be selected, or engineered, to alter the glucan-to-xylan ratio (GXR) but no TEAs have quantified the impact of this strategy systematically. This study explores the cost impacts of varying the glucan-to-xylan ratio (GXR) from 1.9 to 6.7 for co-fermenting glucose and xylose to ethanol and bisabolene. The minimum selling prices (MSPs) for both products decrease as the GXR increases, with the largest reductions at shorter residence times. For instance, with an increase in GXR from 1.9 to 6.7, ethanol’s MSP drops by 16 %, 5 %, and 3 % at 24, 72, and 144 h, respectively, while bisabolene’s MSP declines by 23 %, 20 %, and 15 % at 24, 72, and 120 h. Particularly for early-stage commercialization, the results suggest that altering or selecting for feedstocks with higher GXR can minimize capital costs by reducing optimal residence times. Capital-constrained biorefineries operating with shorter residence times can justify paying up to 1.5X to 2X the price for feedstocks with a higher GXR, based on the expected improvements in their product yield and overall process economics.

Delayed xylose utilization↗
DOE OSTI2021

Toward sustainable, cell-free biomanufacturing

Industrial biotechnology is an attractive approach to address the need for low-cost fuels and products from sustainable resources. Unfortunately, cells impose inherent limitations on the effective synthesis and release of target products. One key constraint is that cellular survival objectives often work against the production objectives of biochemical engineers. Additionally, industrial strains release CO2 and struggle to utilize sustainable, potentially profitable feedstocks. Cell-free biotechnology, which uses biological machinery harvested from cells, can address these challenges with advantages including: (i) shorter development times, (ii) higher volumetric production rates, and (iii) tolerance to otherwise toxic molecules. In this review, we highlight recent advances in cell-free technologies toward the production of non-protein products beyond lab-scale demonstrations and describe guiding principles for designing cell-free systems. Specifically, we discuss carbon and energy sources, reaction homeostasis, and scale-up. Expanding the scope of cell-free biomanufacturing practice could enable innovative approaches for the industrial production of green chemicals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A scalable and tunable thermoreversible polymer for 3D human pluripotent stem cell biomanufacturing

Human pluripotent stem cells (hPSCs) are an exciting and promising source to enable cell replacement therapies for a variety of unmet medical needs. Though hPSCs can be successfully derived into numerous physiologically relevant cell types, effective translation to the clinic is limited by challenges in scalable production of high-quality cells, cellular immaturity following the differentiation process, and the use of animal-derived components in culture. To address these limitations, we have developed a fully defined, reproducible, and tunable thermoreversible polymer for high-quality, scalable 3D cell production. Our reproducible synthesis method enables precise control of gelation temperature (24°C–32°C), hydrogel stiffness (100–4000 Pa), and the prevention of any unintended covalent crosslinking. After material optimization, we demonstrated hPSC expansion, pluripotency maintenance, and differentiation into numerous lineages within the hydrogel. Overall, this 3D thermoreversible hydrogel platform has broad applications in scalable, high-quality cell production to overcome the biomanufacturing burden of stem cell therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Biomanufacturing and self-propulsion dynamics of nanoscale bacteria-enabled autonomous delivery systems

Flagellated bacteria have superb self-propulsion capabilities and are able to effectively move through highly viscous fluid and semi-solid (porous) environments. This innate aptitude has been harvested for whole-cell actuation of bio-hybrid microrobotic systems with applications in directed transport and microassembly. In this work, we present the biomanufacturing of Nanoscale Bacteria-Enabled Autonomous Delivery Systems (NanoBEADS) by controlled self-assembly and investigate the role of nanoparticle load on the dynamics of their self-propulsion in aqueous environments. Each NanoBEADS agent is comprised of spherical polystyrene nanoparticles assembled onto the body of a flagellated Escherichia coli bacterium. We demonstrate that the NanoBEADS assembly configuration is strongly dependent upon the nanoparticles to bacteria ratio. Furthermore, we characterized the stochastic motion of the NanoBEADS as a function of the quantity and size of the nanoparticle load and computationally analyzed the effect of the nanoparticle load on the experienced drag force. We report that the average NanoBEADS swimming speed is reduced to 65% of the free-swimming bacteria speed (31 μm/s) at the highest possible load. NanoBEADS can be utilized as single agents or in a collaborative swarm in order to carry out specific tasks in a wide range of applications ranging from drug delivery to whole cell biosensing.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2017

Industrial biomanufacturing: The future of chemical production

The current model for industrial chemical manufacturing employs large-scale megafacilities that benefit from economies of unit scale. However, this strategy faces environmental, geographical, political, and economic challenges associated with energy and manufacturing demands. We review how exploiting biological processes for manufacturing (i.e., industrial biomanufacturing) addresses these concerns while also supporting and benefiting from economies of unit number. Key to this approach is the inherent small scale and capital efficiency of bioprocesses and the ability of engineered biocatalysts to produce designer products at high carbon and energy efficiency with adjustable output, at high selectivity, and under mild process conditions. The biological conversion of single-carbon compounds represents a test bed to establish this paradigm, enabling rapid, mobile, and widespread deployment, access to remote and distributed resources, and adaptation to new and changing markets.

Science & Technology - Other Topics↗
DOE OSTI2026

Jupyter Notebook Code for “Data-Driven Insights to Accelerate Advanced Biomanufacturing”

This page contains the datasets and code #O5097 Jupyter Notebook Code for “Data-Driven Insights to Accelerate Advanced Biomanufacturing”. Data literature-derived cultivation experiments for polyhydroxybutyrate (PHB) production in Synechocystis sp. PCC 6803 and were used for ML model development, interpretation, and experimental validation.

Lalonde, Jessica N. [Los Alamos National Laborator↗
DOE OSTI2018

Chapter 8: Metabolic Engineering of Methanotrophic Bacteria for Industrial Biomanufacturing

CH4 offers a promising, high-volume petroleum replacement for fuel and chemical bioprocesses. Recent advances in gas recovery technologies have facilitated access to previously inaccessible natural gas reserves, while biogas generated from anaerobic digestion of waste streams offers a versatile, renewable CH4 source. Importantly, CH4 is also the second most abundant greenhouse gas (GHG), with nearly 60% of emissions derived from anthropogenic sources. However, the gaseous state of CH4 makes for a lack of compatibility with current transportation and industrial manufacturing infrastructure, limiting its utilization as a transportation fuel and intermediate in biochemical processes. Resurgent interest in CH4 upgrading has pushed microbial conversion of CH4 to fuels and value-added chemicals to the forefront of industrial bioprocessing. CH4 bioconversion offers both CH4 valorization and GHG emission reduction potential and importantly offers a scalable, modular, and selective approach to CH4 utilization compared to conventional physical and chemical conversion strategies. However, as noted above, advances in CH4 biocatalysis have been constrained by limited genetic tractability of natural CH4-consuming microbes. In this chapter, we review recent advances in methanotrophic genetic and genomic tool development and metabolic engineering.

09 BIOMASS FUELS↗
DOE OSTI2025

From bench to biofactory: high-throughput technologies and automated workflows to accelerate biomanufacturing

Microbial production of target molecules has advanced significantly in recent years driven by innovations in enzyme engineering, DNA synthesis, and genomic editing. However, to access the massive potential of microbial production, a vast parametric space remains to be investigated to optimize these biobased processes for a robust bioeconomy. Here, we review the current state of the art, some key challenges and possible solutions. We see a critical role of automation, high-throughput technologies, self-driving and cloud labs, and data management to enable Artificial Intelligence/Machine Learning and mechanistic models to overcome the design space challenges and accelerate the development of novel bio-based solutions. Accurate models will expedite the development and scale-up of engineered microbes for a range of final products from many starting materials.

Petzold, Christopher J↗
DOE OSTI2025

Engineered Accumulation of Protocatechuate in Corn Biomass to Enhance Biomanufacturing

The in-planta accumulation of coproducts in crops can enhance the value of lignocellulosic biomass and facilitate a sustainable bioeconomy. Corn stover represents a major renewable source of lignocellulose for the production of advanced biofuels and bioproducts. In this study, we engineered corn with a bacterial gene encoding a dehydroshikimate dehydratase (QsuB) to overproduce protocatechuate (DHBA). Transgenic corn lines accumulate up to 2.9% DHBA on a dry weight basis in leaf and stem biomass. DHBA occurs in the form of glucosides that are extractable from biomass using aqueous methanol as the solvent. The analysis of lignin did not show any evidence for the incorporation of DHBA; however, an increase in the lignin syringyl to guaiacyl ratio and a higher relative abundance of p-coumarate groups compared with total lignin units were observed in QsuB-modified corn. Alkaline hydrolysates prepared from QsuB corn were enriched in DHBA compared to the hydrolysates obtained from wild-type biomass, which contained mostly p-coumarate and ferulate. Using engineered Novosphingobium aromaticivorans as a production host, a 375% improvement in 2-pyrone-4,6-dicarboxylate titers was achieved through biological upgrading of alkaline hydrolysates derived from QsuB corn compared to unmodified biomass. Our data demonstrate an engineering strategy to overproduce DHBA in corn that can facilitate sustainable manufacturing of other valuable bioproducts using stover as a feedstock.

2-pyrone-4,6-dicarboxylate↗
DOE OSTI2023

Unravelling the hidden power of esterases for biomanufacturing of short-chain esters

Abstract Microbial production of esters has recently garnered wide attention, but the current production metrics are low. Evidently, the ester precursors (organic acids and alcohols) can be accumulated at higher titers by microbes like Escherichia coli . Hence, we hypothesized that their ‘direct esterification’ using esterases will be efficient. We engineered esterases from various microorganisms into E. coli , along with overexpression of ethanol and lactate pathway genes. High cell density fermentation exhibited the strains possessing esterase-A (SSL76) and carbohydrate esterase (SSL74) as the potent candidates. Fed-batch fermentation at pH 7 resulted in 80 mg/L of ethyl acetate and 10 mg/L of ethyl lactate accumulation by SSL76. At pH 6, the total ester titer improved by 2.5-fold, with SSL76 producing 225 mg/L of ethyl acetate, and 18.2 mg/L of ethyl lactate, the highest reported titer in E. coli . To our knowledge, this is the first successful demonstration of short-chain ester production by engineering ‘esterases’ in E. coli .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Engineering of xylose metabolic pathways in Rhodotorula toruloides for sustainable biomanufacturing

Abstract The oleaginous yeast Rhodotorula toruloides is a promising microbial cell factory for the sustainable production of biofuels and value-added chemicals from renewable carbon sources. Unlike the conventional yeast Saccharomyces cerevisiae, R. toruloides can naturally metabolize xylose, the second most abundant sugar in lignocellulosic hydrolysates. However, its native xylose metabolism is inefficient, characterized by slow xylose uptake and accumulation of D-arabitol. Moreover, despite its phenotype, research on the enzymes involved in xylose metabolism has yet to reach a consensus. Therefore, this review provides a comprehensive analysis of the non-canonical xylose metabolism in R. toruloides, focusing on the properties of key enzymes involved in xylose metabolism. Native xylose reductase and xylitol dehydrogenase exhibit broad substrate promiscuity compared to their counterparts in the xylose-fermenting Scheffersomyces stipitis. Additionally, the absence of xylulokinase expression under xylose-utilizing conditions redirects metabolism toward D-arabitol accumulation. Consequently, D-arabitol dehydrogenases and ribulokinase play essential roles in the xylose metabolism of R. toruloides. These findings highlight the fundamental differences between R. toruloides xylose metabolism and the oxidoreductase pathways observed in other xylose-fermenting yeast, providing insights for metabolic engineering strategies to improve xylose utilization and enhance bioconversion of cellulosic hydrolysates to different bioproducts by R. toruloides.

Biotechnology & Applied Microbiology↗
DOE OSTI2023

Optimization of Spirulina for biomanufacturing and the delivery of protein therapeutics

Lumen Bioscience has developed a novel cyanobacterial platform that enormously decreases the cost of pharmaceuticals used to prevent and treat illnesses. Arthrospira platensis (spirulina), is a photosynthetic microorganism that has been consumed as a dietary supplement for centuries in part because of its high protein content. Commercial cultivation operations have matured over the last 50 years to allow large-scale cultivation in outdoor ponds. Lumen recently discovered methods that transform this commercially important cyanobacterium into a genetically tractable platform for bioengineering. The high protein accumulation in spirulina makes it an ideal chassis for heterologous protein expression, and centuries of safe human consumption suggest its utility as an administration vehicle for biologic drugs. Lumen can express a broad range of recombinant proteins in spirulina and has developed manufacturing processes and strains to mucosally deliver bioactive proteins to treat and/or prevent disease. For example, Lumen has produced an oral cocktail of dried whole-cell spirulina biomass, containing 3 toxin-neutralizing antibodies and 1 endolysin, that is efficacious in a preclinical in vivo models of C. difficile infection. Lumen has also demonstrated that intranasal administration of a spirulina-manufactured neutralizing antibody can prevent disease by a respiratory pathogen, SARS-CoV-2, in a hamster model. Lumen’s current pipeline includes therapeutics to treat or prevent C. difficile infection, COVID-19, inflammatory bowel disease, cardiometabolic disease, and traveler’s diarrhea. Lumen deploys strategies to maximize the expression of these therapeutics for optimal dose sizing, a key limiting factor with past food crop-based expression systems. Spirulina can express exogenous proteins at unusually high levels (>15% of dry weight) but reaching this maximum value requires optimization of multiple interacting factors. We describe our current statistics design of experiments approach that optimizes these factors with minimal replicates. This maximizes exogenous protein expression allowing Lumen to generate spirulina-based therapeutics for a rapidly expanding range of medical uses.

Heinnickel, Mark↗