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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Dawn T
authors.initials: DT
authors.lastname: Eriksen
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Lian
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States. Electronic address: zhao5@illinois.edu.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
mesh_terms: D055162:Biocatalysis; D019149:Bioreactors; D015374:Biosensing Techniques; D003198:Computer Simulation; D019020:Directed Molecular Evolution; D004798:Enzymes / Q000737:chemistry*; D008958:Models, Molecular; D015202:Protein Engineering; D015398:Signal Transduction
chemical_list: D004798:Enzymes
keywords: Biosensors; Directed evolution; Pathway engineering; Protein engineering; Rational design; Synthetic biology
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