Single-cell protein optimizing production

The first persons to point out the possibility of computer monitoring of indirectly measured parameters were Yamashito, Hisashi, and Inagaki in 1969 (2). The method was described in a U.S. Patent in 1975 (3). Examples of the application of computer-aided indirectly measured parameters to the control and optimization of batch-fed Baker s Yeast fermentation were described by Jefferis and Humphrey in 1973 (4) and by Wang, Cooney, and Wang in 1977 (5). Background and detailed history of this application can be found in the review by Humphrey (1). The work to be discussed in this report is another example of computer-aided indirectly measured cell biomass and growth rate and the use of this information in the feed back control of the carbon substrate, ethanol, in a process for the production of a yeast single cell protein (SCP). 

Figure 3. Strategies for optimization of continuous culture for production of single-cell protein. Top, under continuous culture isotherm with a fixed value for carbon source feed concentration. D is the dilution rate of maximum productivity. Bottom, comparison of isotherm for fixed substrate feed concentration. So, with that for fixed oxygen transfer rate, OTR (curves show the maximum cell concentration for a given OTR and cell yield).

The strategy for optimizing single-cell protein production is based not only on a dilution rate that will give a low residual substrate concentration and high conversion yield, but also that will operate with the maximum cell density permitted by the oxygen transfer rate. Simultaneously, it is important to prevent accumulation of residual methanol to achieve both high yields and process stability. 

The use of GHO and NSO cells for the large-scale production of recombinant proteins has been facilitated by the fact that both cell types grow well in single-cell suspension culture with the highest cell densities from an extended batch process reported to be greater than 10 cells mH. This is about five times higher than was seen 20 years ago. Optimized cell lines can achieve secretion of 50 pg per cell per day of recombinant protein. The record on volumetric titer from recombinant mam-... 

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