ePathOptimize: A Combinatorial Approach for Transcriptional Balancing of Metabolic Pathways

Authors
Jones, J. Andrew
Vernacchio, Victoria R.
Lachance, Daniel M.
Lebovich, Matthew
Fu, Li
Shirke, Abhijit N.
Schultz, Victor L.
Cress, Brady
Linhardt, Robert J.
Koffas, Mattheos A.G.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2015-06-11
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
Attribution 3.0 United States
CC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
Full Citation
ePathOptimize: A Combinatorial Approach for Transcriptional Balancing of Metabolic Pathways, J. A. Jones, V. Vernacchio, D.Lachance, M. Lebovich, L. Fu, A. Shirke, V. Schultz, B. Cress, R. J. Linhardt, M. Koffas, Scientific Reports, 5, 11301, 2015.
Abstract
The ability to fine tune gene expression has created the field of metabolic pathway optimization and balancing where a variety of factors affecting flux balance are carefully modulated to improve product titers, yields, and productivity. Using a library of isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible mutant T7 promoters of varied strength a combinatorial method was developed for transcriptional balancing of the violacein pathway. Violacein biosynthesis involves a complex five-gene pathway that is an excellent model for exploratory metabolic engineering efforts into pathway regulation and control due to many colorful intermediates and side products allowing for easy analysis and strain comparison. Upon screening approximately 4% of the total initial library, several high-titer mutants were discovered that resulted in up to a 63-fold improvement over the control strain. With further fermentation optimization, titers were improved to 1829 ± 46 mg/L; a 2.6-fold improvement in titer and a 30-fold improvement in productivity from previous literature reports.
Description
Scientific Reports, 5, 11301
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Nature
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Scientific Reports
https://harc.rpi.edu/
Access
Open Access
CC BY — Creative Commons Attribution