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Mutant Selection - Large scale mutant selection programmes begin when favourable reports of clinical trials are obtained. In the early stages, selection of spontaneous mutants may be helpful, but induced mutations are the most common sources of improvements.

Many mutations bring about marked changes in a biochemical character of practical interest; these are called major mutations. Some major  mutations can be useful in strain improvement.

 

For example, a mutant strain (S-604) of Streptomyces aureofaciens produces 6-demethyl tetracycline in place of tetracycline; this demethylated form of tetracycline is the major commercial form of tetracycline.

In contrast, most improvements in biochemical production have been due to the stepwise accumulation of so called minor genes. These genes lead to small increases (or decreases) in the antibiotic or other biochemical production, and selection may be expected to result in a 10-15% increase in yield.
The selected strains are usually subjected to successive cycles of mutagenesis and selection; after several cycles, a large increase is yield is likely to be obtained. Mutants of Penicillium chrysogenum were selected for increased penicillin production; each cycle of selection was preceded by Mutagen (chemical) treatment and resulted in only small changes in penicillin yield.

 

The two types are associated with different strains of A. tumefaciens. There is also a related disease ("hairy root disease") in which infected tissues proliferate in root tissue and produce an opine. This disease is associated with the bacterium A. rhizogenes.

Formation of opines explains the ecological significance of tumor formation. Each strain of Agrobacterium synthesizes enzymes (permease, dehydrogenase) that allow it to metabolize the specific type of opine formed by the tumor it induces. Thus by stimulating the plant to form opines, the bacteria insure themselves a supply of nutrients specifically designed for them.

After several (about dozen) cycles of selection, a strain (E 15-1) was obtained that yielded 55% more penicillin than the original strain (Fleming strain).