title: Sensitive cells: enabling tools for static and dynamic control of microbial metabolic pathways.
abstract: Natural metabolic pathways are dynamically regulated at the transcriptional, translational, and protein levels. Despite this, traditional pathway engineering has relied on static control strategies to engender changes in metabolism, most likely due to ease of implementation and perceived predictability of design outcome. Increasingly in recent years, however, metabolic engineers have drawn inspiration from natural systems and have begun to harness dynamically controlled regulatory machinery to improve design of engineered microorganisms for production of specialty and commodity chemicals. Here, we review recent enabling technologies for engineering static control over pathway expression levels, and we discuss state-of-the-art dynamic control strategies that have yielded improved outcomes in the field of microbial metabolic engineering. Furthermore, we emphasize design of a novel class of genetically encoded controllers that will facilitate automatic, transient tuning of synthetic and endogenous pathways.
authors.affiliation: Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.
authors.forename: Brady F
authors.initials: BF
authors.lastname: Cress
authors.affiliation: Plant Biochemistry and Biotechnology Laboratory, Department of Agriculture, School of Agriculture and Food Technology, Technological & Educational Institute of Crete, Crete, Greece.
authors.forename: Emmanouil A
authors.initials: EA
authors.lastname: Trantas
authors.affiliation: Plant Biochemistry and Biotechnology Laboratory, Department of Agriculture, School of Agriculture and Food Technology, Technological & Educational Institute of Crete, Crete, Greece.
authors.forename: Filippos
authors.initials: F
authors.lastname: Ververidis
authors.affiliation: Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States; Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.affiliation: Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States; Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States. Electronic address: koffam@rpi.edu.
authors.forename: Mattheos Ag
authors.initials: MA
authors.lastname: Koffas
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D016680:Genome, Bacterial; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways; D014176:Protein Biosynthesis; D014158:Transcription, Genetic