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Balancing relative expression of pathway genes to minimize flux bottlenecks and metabolic burden is one of the key challenges in metabolic engineering. This is especially relevant for iterative pathways, such as reverse β-oxidation (rBOX) pathway, which require control of flux partition at multiple nodes to achieve efficient syn thesis of target products. Here, we develop a plasmid-based inducible system for orthogonal control of gene expression (referred to as the TriO system) and demonstrate its utility in the rBOX pathway. Leveraging effortless construction of TriO vectors in a plug-and-play manner, we simultaneously explored the solution space for enzyme choice and relative expression levels. Remarkably, varying individual expression levels led to substantial change in product specificity ranging from no production to optimal performance of about 90% of the theoretical yield of the desired products. We obtained titers of 6.3 g/L butyrate, 2.2 g/L butanol and 4.0 g/L hexanoate from glycerol in E. coli, which exceed the best titers previously reported using equivalent enzyme combinations. Since a similar system behavior was observed with alternative termination routes and higher-order iterations, we envision our approach to be broadly applicable to other iterative pathways besides the rBOX. Considering that high throughput, automated strain construction using combinatorial promoter and RBS libraries remain out of reach for many researchers, especially in academia, tools like the TriO system could democratize the testing and evaluation of pathway designs by reducing cost, time and infrastructure requirements.more » « less
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Abstract Advances in the understanding of nanoscale ionic processes in solid‐state thin films have led to the rapid development of devices based on coupled ionic–electronic effects. For example, ion‐driven resistive‐switching (RS) devices have been extensively studied for future memory applications due to their excellent performance in terms of switching speed, endurance, retention, and scalability. Recent studies further suggest that RS devices are more than just resistors with tunable resistance; instead, they exhibit rich and complex internal ionic dynamics that equip them with native information‐processing capabilities, particularly in the temporal domain. RS effects induced by the migration of different types of ions, often driven by an electric field, are discussed. It is shown that, by taking advantage of the different state variables controlled by the ionic processes, important synaptic functions can be faithfully implemented in solid‐state devices and networks. Recent efforts on improving the controllability of ionic processes to optimize device performance are also discussed, along with new opportunities for material design and engineering enabled by the ability to control ionic processes at the atomic scale.more » « less
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Abstract Memristors have emerged as transformative devices to enable neuromorphic and in‐memory computing, where success requires the identification and development of materials that can overcome challenges in retention and device variability. Here, high‐entropy oxide composed of Zr, Hf, Nb, Ta, Mo, and W oxides is first demonstrated as a switching material for valence change memory. This multielement oxide material provides uniform distribution and higher concentration of oxygen vacancies, limiting the stochastic behavior in resistive switching. (Zr, Hf, Nb, Ta, Mo, W) high‐entropy‐oxide‐based memristors manifest the “cocktail effect,” exhibiting comparable retention with HfO2‐ or Ta2O5‐based memristors while also demonstrating the gradual conductance modulation observed in WO3‐based memristors. The electrical characterization of these high‐entropy‐oxide‐based memristors demonstrates forming‐free operation, low device and cycle variability, gradual conductance modulation, 6‐bit operation, and long retention which are promising for neuromorphic applications.more » « less
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