Rational membrane engineering for development of industrial platform biocatalysts
Date
2021-12
Authors
Chavez Santoscoy, Miguel Israel
Major Professor
Advisor
Jarboe, Laura R
Phillips, Gregory
Mansell, Thomas
Underbakke, Eric
Shao, Zengyi
Committee Member
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Altmetrics
Abstract
The use of microorganisms to produce valuable molecules has benefited society for thousands of years. The development of science and technology enables bio-production of a greater diversity of molecules. However, economically competitive bio-production requires high production titers. On an industrial scale, microbial toxicity is often found decreasing production titers and, consequently, the promise of the synthetic biology approach towards sustainability. Cell growth and bio-production are inhibited due to various factors, and the most evident is the product accumulation in the fermentation broth. The use of adaptive laboratory evolution generated robust and high-producer microbes towards a set of specific chemicals. Omics technologies constantly showed the main role of the cell membrane for the adaptation and performance of evolved microbes. However, a holistic approach towards robustness across various inhibitory conditions that enhance bio-production capacity is missing. Here, we have hypothesized that rational engineering targeting the cell membrane of biocatalysts will enhance their robustness and production capacity towards a wide range of molecules. After having executed four independent studies, our overall results support our initial hypothesis and point the field of metabolic engineering (or synthetic biology) towards membrane engineering for improving microbial performance. We anticipate that further efforts within the emerging field of membrane engineering will drive the development of synthetic biology towards economically competitive and sustainable bio-production.
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dissertation