Protein design for pathway engineering |
| |
| Institution: | 1. Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;2. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;3. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;4. Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;1. Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 Tübingen, Germany;2. Milwaukee School of Engineering, Physics and Chemistry Department, 1025 N Broadway, Milwaukee, WI 53202, USA;1. Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, Italy;2. CASPUR Inter-universities Consortium for Supercomputing Applications, Via dei Tizii 6b, Rome 00185, Italy;1. Department of Physics, The City College of New York, New York, NY 10031, United States;2. Department of Biochemistry, The City College of New York, New York, NY 10031, United States;3. Department of Chemistry, The University of Western Ontario, Ontario, Canada;1. Department of Computer Science, Tufts University, Medford, MA 02155, United States;2. Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155, United States |
| |
| 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. |
| |
| Keywords: | Protein engineering Directed evolution Rational design Pathway engineering Synthetic biology Biosensors |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
