Escherichia coli HGT: Engineered for high glucose throughput even under slowly growing or resting conditions

- E. coli HGT strain, a novel platform offering high glucose uptake, was engineered.
- Strongly elevated glucose consumption even under slow or non-growing conditions.
- Under N-limitation, E. coli HGT exceeds cell-specific WT rates in about three-fold.
- The WT-like oxygen needs of HGT makes it applicable to large-scale cultivations.
- E. coli HGT represents a host for pyruvate-derived downstream product synthesis.

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 (0.6 gGlc gCDW−1 h−1) compared to that of wild type, with a maximum glucose uptake rate of about 1.8 gGlc gCDW−1 h−1 already at a 0.3 h−1 specific 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.