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Life Sciences

Washington University in St. Louis

Theses/Dissertations

Metabolic Engineering

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Understanding Control Of Metabolite Dynamics And Heterogeneity, Christopher John Hartline Aug 2022

Understanding Control Of Metabolite Dynamics And Heterogeneity, Christopher John Hartline

McKelvey School of Engineering Theses & Dissertations

Microbes live in complex and continually changing environments. Rapid shifts in nutrient availability are a common challenge for microbes, and cause changes in intracellular metabolite levels. Microbial response to dynamic environments requires coordination of multiple levels of cellular machinery including gene expression and metabolite concentrations. This coordination is achieved through metabolic control systems, which sense metabolite concentrations and direct cellular activity in response. Several reoccurring control architectures are found throughout diverse metabolic systems, which suggests underlying evolutionary advantages for using these control systems to coordinate metabolism. One common, yet understudied, control architecture is the positive feedback metabolite uptake loop, which …


Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz Dec 2021

Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz

McKelvey School of Engineering Theses & Dissertations

Cell-to-cell variation in gene expression and metabolite levels have a significant impact on ensemble productivity of microbial bioproduction. New metabolic engineering tools and approaches are needed that consider cell cultures as an amalgam of uniquely behaving individuals to improve the slow commercialization of metabolically engineered systems. Stochastic cellular process including gene expression, metabolism, and growth lead to phenotypic variation between genetically identical cells. Understanding and the ability to control microbial phenotypic variation is key to improving microbial bioproduction metrics. During protein translation, codon usage strongly influences ensemble gene expression but the effect on the variation of gene expression was not …


Sustainable Bioproduction By Rhodopseudomonas Palustris Tie-1 Through Metabolic Engineering, Wei Bai Jan 2021

Sustainable Bioproduction By Rhodopseudomonas Palustris Tie-1 Through Metabolic Engineering, Wei Bai

McKelvey School of Engineering Theses & Dissertations

The heavy reliance of the petroleum industry for raw material and the rising atmospheric CO2 caused by this reliance have driven the research and development of sustainable alternatives. Microbial production of chemicals, such as fuel and plastic, has been viewed as a feasible method. The wide selection of substrates by microbes enables them to produce chemicals using naturally abundant material or industrial waste, such as CO2, making the production sustainable. Compared to the model organisms such as Escherichia coli, Saccharomyces cerevisiae, many non-model organisms have a broader selection for carbon, electron, and nitrogen sources, making them great candidates for sustainable …


Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin Aug 2019

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …


Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin Aug 2019

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …