Abstract
Nature has an impressive track record of finding creative solutions to problems. These remarkable strategies have presented scientists with many of the best tools for biotechnology, from molecules that target debilitating diseases to extraordinary materials that constantly push boundaries of functionality to microbial cell factories that may one day supplant harmful chemical manufacturing. One of the great missions of scientists is to find and understand how to use these tools. Microbial cell factories represent an alternative pathway to the manufacture of the chemicals that make our modern world function. Traditionally these chemicals are derived from petroleum and have a devastating impact on our planet and human health. The fields of systems biology, synthetic biology, metabolic engineering, bioengineering, and biochemistry are among the fields that specialize in engineering biology toward sustainable biomanufacturing. Researchers in these fields have a broad and ever-expanding toolbox of microbes, genetic elements, and techniques that can be applied to generate the systems that will bring this future into fruition. Learning from what nature has already done to be able to adapt these tools for biotechnology is a core tenet of this dissertation. Traditionally, a cadre of well-characterized and well-engineered organisms have been used in the fields of synthetic biology, metabolic engineering, and bioengineering. These organisms have the advantage of decades of research and while there is always more to be learned, the capabilities, limitations, metabolic functions, and physiology are built on a deep foundation of knowledge. New and exciting organisms garner interest often, though biotechnology efforts are hindered by the limited foundational knowledge that informs engineering efforts. V. natriegens is one such exciting organism. Originally gaining notoriety as a non-pathogenic organism with an extremely fast growth rate, research into V. natriegens has grown phenomenally since around 2016. This dissertation presents the application of genome-scale model assessment of V. natriegens along with LLM-enabled knowledge networking to assess the capabilities and drawbacks of this organism within the realms of synthetic biology tool development, systems biology interrogation, biomanufacturing of valuable chemicals, and microbial ecology. The assessment is critical for understanding the V. natriegens research landscape and mapping the bright future of this organism for biotechnology. As a promising biotechnology platform organism with limited systems biology study, building understanding of V. natriegens from a variety of angles is important, especially under such conditions that are relevant industrially and are not well characterized. This dissertation expands the systems biology interrogation of V. natriegens through a multi-omics lens, applying 13C-metabolic flux analysis (13C-MFA), RNA-seq, genome-scale modeling (GSM), and metabolomics to V. natriegens utilizing acetate and when under reduced NaCl conditions. Acetate is a carbon feedstock that can be made sustainably via CO2 reduction reactions (CO2RR) where atmospheric CO2 is captured and electrochemically converted into a carbon source for heterotrophic microbes that are capable of utilizing it, like V. natriegens. Acetate has potential as an industrial feedstock due to the cost-effective nature of production and non-food-based origins. High NaCl concentrations in industrial bioproduction is a concern for corrosion. As a halophilic organism originally isolated from a salt marsh, V. natriegens culture medium typically contains high salt content which may pose a hazard to its industrial uptake. Through a deepening in the understanding of the metabolism under each of these industrially relevant conditions through a multi-omics approach, V. natriegens is moved closer to its full realization as a platform for biotechnology.
Committee Chair
Yinjie Tang
Committee Members
Himadri Pakrasi, Doug Allen; Fuzhong Zhang; Joshua Yuan
Degree
Doctor of Philosophy (PhD)
Author's Department
Energy, Environmental & Chemical Engineering
Document Type
Dissertation
Date of Award
4-29-2026
Language
English (en)
DOI
https://doi.org/10.7936/yk27-fs14
Recommended Citation
Lima, Matthew, "Building a Systems-Level Understanding of Vibrio natriegens for Bioengineering" (2026). McKelvey School of Engineering Graduate Student Theses & Dissertations. 1377.
The definitive version is available at https://doi.org/10.7936/yk27-fs14