D

Fig. 2.10. The effect of D on steady-state product concentration (p) and product output (Dp) when:

(a) qp is growth related.

when qp is growth-related the advantage of high productivity obtained at high dilution rates must be balanced against the disadvantage of low product concentration resulting in increased downstream processing costs. The other arguments presented for the superiority of continuous culture for biomass production also hold true for product synthesis — ease of automation and the.advantages of steady state conditions. The question that then arises is 'Why has the fermentation industry not adopted continuous culture for the manufacture of microbial products?' It can be appreciated that the arguments cited previously against continuous culture (contamination and equipment reliability) are not valid as these difficulties have been overcome in the large-scale continuous biomass processes. The answer to the question lies in the highly selective nature of continuous culture. We have already seen that ¡jl is determined by D in a steady state chemostat and that M and D are related to substrate concentration according to the equation:

The effect of substrate concentration on specific growth rate for two organisms, A and B, is shown in Fig. 2.11. A is capable of growing at a higher specific growth rate at any substrate concentration. The self-balancing properties of the chemostat mean that the organism reduces the substrate concentration to the value where fi = D. Thus, at dilution rate X, organism A would reduce the substrate concentration to Z. However, at this substrate concentration, organism B could grow only at a ¡x of Y. Therefore, if organisms A and B were introduced into a chemostat operating at dilution rate X, A would reduce the substrate concentration to Z at which B could not maintain a /x of X and would be washed out at a rate of (X - Y) and a monoculture of A would be established eventually. The same situation would occur if A and B were mutant strains arising from the same organism. Commercial organisms have been selected and mutated to produce metabolites at very high concentrations (see Chapter 3) and, as a result, tend to grow inefficiently with low ju.max values and, possibly, high Ks values. Back mutants of production strains produce much lower concentrations of product and, thus, grow more efficiently. If such back mutants arise in a chemostat industrial process, then the production strain will be displaced from the fermentation as described in the foregoing scenario.

Calcott (1981) described this phenomenon as "contamination from within" and this type of 'contamination' cannot be solved by the design of more 'secure' fermenters. Thus, it is the problem of strain degeneration which has limited the application of large scale continuous culture to biomass and, to a lesser extent, potable and industrial alcohol. The production of alcohol by continuous culture is feasible because it is a byproduct of energy generation and, thus, is not a drain on the resources of the organism. However, it is possi-

1 Residual substrate concentration

Fig. 2.11. Competition between two organisms in a chemostat.

1 Residual substrate concentration

Fig. 2.11. Competition between two organisms in a chemostat.

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