A systems biology approach to understanding and improving butanol production in clostridium beijerinckii

Systems Biology;Clostridium beijerinckii;Butanol;Constraint-based Modeling;Metabolomics

Porter, Caroline

关键词: Systems Biology;    Clostridium beijerinckii;    Butanol;    Constraint-based Modeling;    Metabolomics;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/46844/Caroline_Porter.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Solventogenic clostridia offer a sustainable alternative to petroleum-based production of butanol—an important chemical feedstock and potential fuel additive or replacement.Clostridium beijerinckii is an attractive microorganism for butanol production because it (1) naturally produces the highest recorded butanol concentrations as a byproduct of fermentation; and (2) can co-ferment pentose and hexose sugars (the primary products from lignocellulosic hydrolysis).Prior to my Ph.D. work, C. beijerinckii metabolism had been primarily studied from a reductionist perspective, with research focused on a handful of pathways, reactions, and phenotypes. Interrogating the metabolism of this microorganism using a systems biology approach broadens this perspective to study the global effects of genetic and environmental perturbations.For my Ph.D. dissertation, I used constraint-based modeling and metabolic profiling to holistically investigate C. beijerinckii metabolism, with the ultimate goal of garnering new insights to guide strain design for increased butanol production. The work described herein makes four important contributions to advance C. beijerinckii research: (1) the first constraint-based genome-scale model of C. beijerinckii metabolism (iCM925) and demonstration that constraint-based analysis of iCM925 can accurately reproduce physiological behavior and provide insight into the underlying mechanisms of microbial butanol production; (2) hypothesis generation using model iCM925 for alternative acetate production mechanisms in mutant strain pta::int(17); (3) model-guided knockout candidates for improved butanol production; (4) the first time-series metabolomics study for C. beijerinckii, used to identify distinct metabolic phases and suggest new metabolite annotations.Going forward, it is my hope that the research presented herein will serve as a launching pad to systemic C. beijerinckii research endeavors. Model iCM925 offers a useful tool to researches wishing to better understand C. beijerinckii metabolic behavior and metabolically engineer C. beijerinckii for sustainable production of fuels and chemicals. The metabolomics study provides novel insight into the dynamic changes occurring over the C. beijerinckii life cycle that can be used for hypothesis generation in future experiments. Systems-based approaches to understanding and manipulating metabolism such as those employed here are important in the on-going efforts to develop predictive and informative tools to study high-throughput data types in both industrial biotechnology and biomedicine.