Investigating Non-model Microorganisms for Biomanufacturing via Systems Biology and Machine Learning

Non-model microorganisms are becoming promising biomanufacturing chassis well-suited for production of sustainable oleochemicals. The expansion of synthetic biology tools has allowed for efficient redirection of carbon towards products, generating numerous production strains at the laboratory scale. However, selecting gene engineering targets is non-trivial, as lessons learned from previous microbes are not always applicable. Additionally, promising laboratory strains routinely fail to maintain performance during scale-up, requiring strain re-engineering and leading to significant commercialization risk. There is a need for characterization of the functional metabolism of non-model engineered strains as well as new computational design algorithms that can generate robust strains and link complex omics data to cellular regulatory processes. Current models inadequately capture the environmental stresses which contribute to loss of production during scale-up while the physiological responses over the course of long-cultivations in reactors remain poorly understood. This dissertation broadly focused on improving microbial systems for industrial applications and aimed to address current limitations by 1. identifying engineered strain bottlenecks using metabolomics and 13C-isotopic tracing, 2. developing a data-driven modeling framework integrated with mechanistic genome-scale modeling for engineered yeast performance prediction and strain design, and 3. expanding genome-scale modeling techniques for 13C flux analysis.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Energy, Environmental & Chemical Engineering

Year dc:date.available

2021

Author dc:creator

• Czajka, Jeffrey John

Contributors dc:contributor

• Yinjie J Tang
• Doug Allen

• Chemical Engineering

Statement dc:rights

• I have not registered my thesis with the U.S. Copyright Office, and do not intend to.

Language dc:language

English (en)

Identifier

https://openscholarship.wustl.edu/eng_etds/722

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:eng_etds-1774