Journal
BIOTECHNOLOGY JOURNAL
Volume 8, Issue 12, Pages 1397-1410Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.201300021
Keywords
Directed evolution; Metabolic engineering; Pathway engineering; Synthetic biology
Funding
- DuPont Young Professor Grant
- Office of Naval Research Young Investigator Program Award
- DARPA Living Foundries program [HR0011-12-C-0066]
- National Science Foundation [CBET-1067506]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1067506] Funding Source: National Science Foundation
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Cellular systems can be engineered into factories that produce high-value chemicals from renewable feedstock. Such an approach requires an expanded toolbox for metabolic engineering. Recently, protein engineering and directed evolution strategies have started to play a growing and critical role within metabolic engineering. This review focuses on the various ways in which directed evolution can be applied in conjunction with metabolic engineering to improve product yields. Specifically, we discuss the application of directed evolution on both catalytic and non-catalytic traits of enzymes, on regulatory elements, and on whole genomes in a metabolic engineering context. We demonstrate how the goals of metabolic pathway engineering can be achieved in part through evolving cellular parts as opposed to traditional approaches that rely on gene overexpression and deletion. Finally, we discuss the current limitations in screening technology that hinder the full implementation of a metabolic pathway-directed evolution approach.
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