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Title: Protein design for pathway engineering

Abstract

Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. (C) 2013 Elsevier Inc. All rights reserved.

Authors:
; ;
Publication Date:
Sponsoring Org.:
USDOE Advanced Research Projects Agency - Energy (ARPA-E)
OSTI Identifier:
1211080
DOE Contract Number:  
DE-AR0000206
Resource Type:
Journal Article
Journal Name:
Journal of Structural Biology
Additional Journal Information:
Journal Volume: 185; Journal Issue: 2; Journal ID: ISSN 1047-8477
Country of Publication:
United States
Language:
English

Citation Formats

Eriksen, DT, Lian, JZ, and Zhao, HM. Protein design for pathway engineering. United States: N. p., 2014. Web. doi:10.1016/j.jsb.2013.03.011.
Eriksen, DT, Lian, JZ, & Zhao, HM. Protein design for pathway engineering. United States. https://doi.org/10.1016/j.jsb.2013.03.011
Eriksen, DT, Lian, JZ, and Zhao, HM. 2014. "Protein design for pathway engineering". United States. https://doi.org/10.1016/j.jsb.2013.03.011.
@article{osti_1211080,
title = {Protein design for pathway engineering},
author = {Eriksen, DT and Lian, JZ and Zhao, HM},
abstractNote = {Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. (C) 2013 Elsevier Inc. All rights reserved.},
doi = {10.1016/j.jsb.2013.03.011},
url = {https://www.osti.gov/biblio/1211080}, journal = {Journal of Structural Biology},
issn = {1047-8477},
number = 2,
volume = 185,
place = {United States},
year = {Sat Feb 01 00:00:00 EST 2014},
month = {Sat Feb 01 00:00:00 EST 2014}
}