Modeling of Overflow Metabolism in Batch and Fed-Batch Cultures of Escherichia coli

Abstract

A dynamic model of glucose overflow metabolism in batch and fed-batch cultivations of Escherichia coli W3110 under fully aerobic conditions is presented. Simulation based on the model describes cell growth, respiration, and acetate formation as well as acetate reconsumption during batch cultures, the transition of batch to fed-batch culture, and fed-batch cultures. E. coli excreted acetate only when specific glucose uptake exceeded a critical rate corresponding to a maximum respiration rate. In batch cultures where the glucose uptake was unlimited, the overflow acetate made up to 9. 0 +/- 1.0% carbon/carbon of the glucose consumed. The applicability of the model to dynamic situations was tested by challenging the model with glucose and acetate pulses added during the fed-batch part of the cultures. In the presence of a glucose feed, E. coli utilized acetate 3 times faster than in the absence of glucose. The cells showed no significant difference in maximum specific uptake rate of endogenous acetate produced by glucose overflow and exogenous acetate added to the culture, the value being 0.12-0.18 g g-1 h-1 during the entire fed-batch culture period. Acetate inhibited the specific growth rate according to a noncompetitive model, with the inhibition constant (ki) being 9 g of acetate/L. This was due to the reduced rate of glucose uptake rather than the reduced yield of biomass.

Model Predictive Feeding Rate Control in Conventional and Single-use Lab-scale Bioreactors: A Study on Practical Application

“…For substrate consumption and biomass growth modeling, mechanistic terms for substrate (glucose) limitation as well as substrate and biomass inhibition were chosen. Substrate limitation and inhibition in batch/fed-batch E. coli cultivation processes are extensively investigated phenomena, described by many authors (e.g., Xu et al 14 ). The applied biomass inhibition term Kx max comes from the logistic law 15 .…”

“…For selection of the reference profile as well as for on-line process modeling in the first experiment (EXP-1), the model parameters from a priori knowledge 14,15,19 were used. Initial values for the limitation and inhibition model parameters were taken from Xu et al 14 ; for biomass inhibition parameter Kx, the initial value was equal to the maximal biomass concentration achieved in E. coli B culture, 86 g L -1 , (Lee 20 ).…”

“…Initial values for the limitation and inhibition model parameters were taken from Xu et al 14 ; for biomass inhibition parameter Kx, the initial value was equal to the maximal biomass concentration achieved in E. coli B culture, 86 g L -1 , (Lee 20 ). After parameter tuning (model fitting to experimental data) in subsequent experiments, the parameter values shown in Table 2 were used in further process modeling.…”

Induction of Viable but Non-culturable (VBNC) State in <i>Salmonella</i> Cultured in M9 Minimal Medium Containing High Glucose

“…[28][29][30] Cerca et al reported that Staphylococcus epidermidis enters the VBNC state in biofilms as a consequence of the accumulation of acidic metabolites due to excessive glucose metabolism 31) ; and several other reports [28][29][30] showed that acetate accumulates in aerobic cultures due to the overflow of glucose metabolism. Our study also obtained similar results: excessive glucose metabolism in 0.8% M9 medium led to the accumulation of large amounts of acidic compounds such as acetic acid, resulting in a sudden decrease in pH, probably due to the overwhelming of the buffering effect of M9 medium (Fig.…”

Multiple model approach to modelling of Escherichia coli fed-batch cultivation extracellular production of bacterial phytase

“…The whole E. coli growth process can be divided into at least four functional states, according to the physiological behaviour of the microorganisms in the process (Zhang et al 1994;Xu et al 1999a;Xu et al 1999b;Zelic et al 2004). …”