Production process monitoring by serial mapping of microbial carbon flux distributions using a novel sensor reactor approach: I - Sensor reactor system

A novel Sensor Reactor technology is presented which permits (13)C labeling experiments for metabolic flux analysis during large-scale, semi-industrial, (fed-) batch fermentation processes deriving a series of flux maps that document fermentation courses in detail. The small-scale Sensor Reactor can be inoculated within 1.50-1.20 s via a special inoculation unit with an inoculation volume accuracy of 1.025 +/- 0.021 L. The large-scale production reactor (here: 300 L) and the Sensor Reactor were run in parallel master/ slave modes to control the current pH, temperature, pressure and dissolved oxygen values as changing set points for the Sensor Reactor. Using an automated pulsing technology, glucose pulses of 5 g/L could be realized within 0.51 s. The similarity of fermentations in the Sensor Reactor with the production process was demonstrated by studying L-lysine production with C. glutamicum during multiple, 'simulated' labeling experiments each lasting 2.5 h. 'Real' labeling experiments are presented in Part II. (C) 2003 Elsevier Science (USA). All rights reserved.