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Fig. 3.4. The spread in chlortetracycline productivity of the survivors of a UV-treated population of Streptomyces viridifaciens (Dulaney and Dulaney, 1967).

tions are deleterious to the yield of the desired product but, as shown in Fig. 3.3, a minority are more productive than the parent. The problem of obtaining the high-yielding mutants may be approached from two theoretical standpoints; the number of desirable mutants may be increased by 'directed mutation', i.e. the use of a technique which will preferentially produce particular mutants at a high rate; or techniques may be developed to improve the separation of the few desirable types from the large number of mediocre producers.

Inherent in the concept of directed mutation is the assumption that a mutation programme can be optimized to produce mutants of a particular kind. The choice of mutagen was demonstrated to affect the success of mutation programmes early in the history of strain improvement schemes. For example, Hostalek (1964) claimed that ultraviolet radiation was the most effective mutagen for increasing the yield of tetracycline by strains of Streptomyces aureofaciens. DeWitt et al. (1989) emphasized that as well as certain mutagens being more beneficial, the dose will affect the generation of the desired types. Despite these observations it is frequently the case that it is difficult to predict what type of mutation is required at the molecular level to improve a strain, and therefore it is extremely unlikely that the concept of directed mutation can be applied in these circumstances. Thus, it is the second approach specified above that is likely to provide the solution to this type of problem, i.e. the development of selection techniques.

i Ik' concept of directed mutation is of "'T'li'lc u'levance when the genes to be modified

0,'T n -nul tlie uranism is genetically well docu-

1,rL 'iTsiiôiilc et al., 1981). In these systems a cloned mented • ^ bc subjected to in vitro enzymatic

1)VA m.) ^ |nanjpuiation such that the mutation is cleavag^. ^ !icil[ar site. Thus, reintroduction of the

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