title: Escherichia coli HGT: Engineered for high glucose throughput even under slowly growing or resting conditions.
abstract: Aerobic production-scale processes are constrained by the technical limitations of maximum oxygen transfer and heat removal. Consequently, microbial activity is often controlled via limited nutrient feeding to maintain it within technical operability. Here, we present an alternative approach based on a newly engineered Escherichia coli strain. This E. coli HGT (high glucose throughput) strain was engineered by modulating the stringent response regulation program and decreasing the activity of pyruvate dehydrogenase. The strain offers about three-fold higher rates of cell-specific glucose uptake under nitrogen-limitation (0.6gGlcgCDW-1h-1) compared to that of wild type, with a maximum glucose uptake rate of about 1.8gGlcgCDW-1h-1already at a 0.3h-1specific growth rate. The surplus of imported glucose is almost completely available via pyruvate and is used to fuel pyruvate and lactate formation. Thus, E. coli HGT represents a novel chassis as a host for pyruvate-derived products.
authors.affiliation: University of Stuttgart, Institute of Biochemical Engineering, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Michalowski
authors.affiliation: University of Stuttgart, Institute of Biochemical Engineering, Allmandring 31, 70569, Stuttgart, Germany. Electronic address: siemann@ibvt.uni-stuttgart.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Siemann-Herzberg
authors.affiliation: University of Stuttgart, Institute of Biochemical Engineering, Allmandring 31, 70569, Stuttgart, Germany. Electronic address: takors@ibvt.uni-stuttgart.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Takors
mesh_terms: D061249:Batch Cell Culture Techniques / Q000379:methods*; D019149:Bioreactors / Q000382:microbiology; D053898:Biosynthetic Pathways / Q000235:genetics; D049109:Cell Proliferation / Q000502:physiology*; D004926:Escherichia coli / Q000502:physiology*; D024861:Genetic Enhancement / Q000379:methods*; D005947:Glucose / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D019289:Pyruvic Acid / Q000378:metabolism*
chemical_list: D019289:Pyruvic Acid; D005947:Glucose
keywords: Escherichia coli; High glucose uptake; Nitrogen-limitation; Stringent response; ppGpp