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On-line Bioprocess Control in Streptomyces spp.
Cultivations based on Dialysis Sampling Method
C. Helbig, T. Bchner, P. Gpel, M. Beuse

Introduction

Glucose is the most important nutrient source for Streptomyces spp.. The production of antibiotics after the exponential growth-phase in cultivations of Streptomyces spp. can be optimised by regulation of the glucose concentration in the media. Therefore comprehensive on-line monitoring of glucose is needed.


Methods

Streptomyces spp. cultivations with different feeds of glucose have been carried out in a 15 litres working volume bio-reactor (Biostat C, B. Braun Biotech Int.). Glucose concentrations in the complex media have been determined on-line with ProcessTRACE in combination with a dialysis probe (TRACE Analytics).

Bioreactor
Fig. 1: Bioreactor connected to ProcessTRACE via dialysis probe.

The concentrations have been verified off-line by analysis with a hexokinase test-kit (Sigma Diagnostics). A schematic view on the experimental set-up is shown in figure 1.


Results

Figure 2 shows a comparison of the on-line and off-line data of the glucose concentrations along with the product concentration during one cycle of a repeated batch fermentation. The productivity is at its maximum. Figure 3 shows the same comparison in a batch fermentation over a period of 110 h.


Fig. 2: Glucose and product concentrations over a period of 100 h cultivation time of S. natalensis.


Discussion

Figure 2 and 3 show that the on-line monitoring with dialysis sampling method leads to data

Fig. 3: Concentrations of glucose analysed on- and off-line in a batch-fermentation of S. conglubatus.


for glucose concentrations, which correlate very well with the data from the off-line analysis. Over a period of more than 100 h no significant difference between on-line and off-line data is observed. Because of zero-volume sampling the probe is particularly suitable for small-scale fermenters in the field of research and process development. As it is possible to get data in very small intervals, a regulation of glucose concentrations in the cultivation vessel reacts very fast. With ProcessTRACE it is possible to detect glucose as well as lactate or methanol on-line in cultivations of other species.


Reference: Tollnick, C.; Beuse, M. (1999): Complete process monitoring; Chemical plants + processing, (4), 50-51.




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