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Biology subjects

Euler, C.

Publications and source records attributed to Euler, C..

4 recordsLinked to original sources

Establishing Vibrio natriegens as a high-performance host for acetate-based poly-3-hydroxybutyrate production

Acetate can be a sustainable and renewable carbon source which holds significant promise for biotechnological production but is underutilized industrially due to limited microbial efficiency. Vibrio natriegens, recognized for exceptionally fast growth rates, represents a compelling host for developing efficient acetate-based bioprocesses. In this study, adaptive laboratory evolution significantly enhanced V. natriegens ability to grow on acetate as the sole carbon source, achieving an 89% increase in growth rate. Genetic and transcriptomic analyses revealed key adaptations improving acetate uptake and metabolism via increased salt tolerance, boosted Pta/AckA pathway activity, and rewired quorum sensing. Further metabolic engineering and bioprocess optimization enabled the evolved strain to reach high cell densities and efficiently convert acetate into the bioplastic poly-3-hydroxybutyrate (PHB), with productivities up to 0.27 g/L/h and PHB accumulation reaching 45.66% of cell biomass. These advances position V. natriegens as a highly promising microbial platform for sustainable, scalable, and cost-effective biomanufacturing using acetate as green feedstock. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/661028v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@ebd5b0org.highwire.dtl.DTLVardef@11a28bforg.highwire.dtl.DTLVardef@6950aforg.highwire.dtl.DTLVardef@303d7b_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

Mixotrophy for carbon-conserving waste upcycling

Modern chemical production, on which human quality of life depends, is unsustainable. Alternative, sustainable manufacturing routes must therefore be developed. Electrochemical and biological processes offer promise for upgrading waste streams, including recalcitrant carbon dioxide and plastic-derived wastes. However, these processes are challenged by the inherent heterogeneity and high energy input requirements for upcycling of the chemical endpoints of the "take-make-waste" economy. Cupriavidus necator is emerging as a potentially useful catalyst to valorize such complex feedstocks because of its extreme metabolic flexibility, which allows it to utilize a wide array of substrates, and its ability to use carbon dioxide directly via the Calvin-Benson-Bassham cycle. C. necator natively oxidizes hydrogen to power carbon utilization, but its inherent flexibility offers an as-yet unexplored opportunity to couple waste stream oxidation with carbon dioxide utilization instead, potentially enabling carbon conservative waste upcycling. Here, we uncover the constraints on carbon conservative chemical transformation using C. necator as a model. We systematically examine the carbon yield and thermodynamic feasibility of mixotrophic scenarios that combine waste-derived carbon sources with hydrogen oxidation to power carbon reassimilation. Then, we evaluate carbon-carbon mixotrophic scenarios, with one carbon source providing electrons in place of hydrogen oxidation. We show that both hydrogen and ethylene glycol have high potential as electron sources to drive carbon-neutral or carbon-negative mixotrophic upgrading of waste streams such as acetate or butyrate. In contrast, we find that carbon conservation is likely infeasible for most other waste-derived carbon sources. This work provides a roadmap to establishing novel C. necator strains capable of carbon efficient waste upcycling.

bioengineering↗

Context-Dependent Flux Coupling via Conserved Small-Molecule Regulatory Structures

Small-molecule regulation modulates enzyme activity and is widespread in metabolic networks. However, the organization of small-molecule regulatory networks and its generalized role is not well understood. We analyze the structure of the genome-wide Escherichia coli small-molecule regulatory network (SMRN) to reveal that it optimizes controllability in the metabolic network. This is achieved by conserved, highly overabundant incoherent feedforward loops. Using multi-omics data, we characterize loop examples in central carbon metabolism. These use signals from hypothesized flux-sensing metabolites phosphoenolpyruvate, -ketoglutarate, citrate, and malate to distinguish between glycolysis, gluconeogenesis, and glyoxylate shunt activity to differentially couple fluxes across these major modes of metabolism. Our results suggest that coupling of fluxes by direct modulation of enzyme activity is an emergent property of the SMRN that depends heavily on both regulatory structure and metabolic context via the metabolome, and further that flux sensing and coupling may be a global property of the metabolic network.

bioengineering↗

Thermodynamic constraints are sufficient for the emergence of flux sensors in metabolism

Metabolism is a precisely coordinated phenomenon, the apparent goal of which is to balance fluxes to maintain robust growth. However, coordinating fluxes requires information about rates, which is not obviously reconcilable with known regulatory mechanisms in which concentrations are sensed through metabolite binding. While flux sensor examples have been characterized, the fundamental principles underlying the phenomenon in general are not well understood. Specifically, the questions of which fluxes can be sensed, and the mechanism by which they are remain open. We address this by showing that the concentrations of substrates of thermodynamically constrained reactions reflect upstream flux and therefore carry information about rates which can be propagated through regulatory interactions to control other fluxes in the network. Using fluxomic, metabolomic, and thermodynamic data in E coli, we show that the concentrations of a few metabolites in central carbon metabolism reflect their producing fluxes and demonstrate that they can transmit information about these rates because of their positions in the network and their roles as effectors.

systems biology↗