Mutant Nutritional

The introduction of techniques for mutagenesis by UV irradiation or by the use of chemicals considerably extended the applications of microbial studies to nutrition (Davis, 1954-1955). Auxotrophic mutants were produced with nutrient dependencies not shown in the untreated parental strains (Beadle and Tatum, 1940). The fortuitous discovery of penicillin by Fleming and its successful use in the treatment of infections (Florey) promoted exhaustive research into its mode of action. Eventually it was established that penicillin prevented the proliferation of gram-positive bacteria by blocking the synthesis of their cell walls... 

Tests for mutation in Aspergillus nidulans are performed in hquid suspension. Conidia are exposed to the test substance both with and without metabohc activation and plated on selective medium to determine changes in colonial morphology or nutritional requirements. At the end of a suitable incubation period, mutant colonies are counted and compared to the number of spontaneous mutants in an untreated control culture. Simultaneous determination of survival... 

Kao, P-T., and T.T. Puck. Genetics of somatic mammalian cells. VII. Induction and isolation of nutritional mutants in Chinese hamster cells. Proc. Natl. Acad. Sci. U.S.A. 60 1275-1281, 1968. 

The first two of these pathways were for many years generally postulated, on the basis of structural relations among various natural products and by analogy with known laboratory reactions they received experimental support later. The last pathway was discovered by B. D. Davis in his work with nutritionally deficient, microbial mutants. However, even earlier, when the structures of quinic acid (VII) and shikimic acid were established, their possible functions as intermediates in the biosynthesis of aromatic... 

Sveshnikov, D., Sveshnikova, N., Rao, K., Hall, D. (1997). Hydrogen metabolism of mutant forms of Anabaena variabilis in continuous cultures and under nutritional stress. FEES Lett. 147,297-301. 

Breakdown of isoleucine, valine, threonine, and methionine results in the production of propionyl-CoA. Propionyl-CoA, in turn, is catabolized to succinyl-CoA via the intermediate methylmalonyl-CoA. Methylmalonyl-CoA is a compoimd of imusual interest to nutritional scientists. This compound accumulates in the cell during a vitamin B12 deficiency. Vitamin B12 deficiency is not a rare disease, as it appears in a common autoimmune disease called pernicious anemia. Vitamin B12 deficiency also occurs in strict vegetarians who avoid meat, fish, poultry, and dairy products. Methylmalonyl-CoA can also build up with rare genetic diseases that involve the production of defective, mutant forms of methylmalonyl-CoAmutase. Most of the methylmalonyl-CoAthat accumulates to abnormally high levels in the cell is hydrolyzed to methylmalonic acid (MMA), which leaves the cell for the bloodstream and eventual excretion in the urine. Some of the MMA is converted back to propionyl-CoA, resulting in the production and accumulation of propionic acid in the cell. The measurement of plasma and urinary MMA has proven to be a method of choice for the diagnosis of vitamin B12 deficiency, whether induced by pernicious anemia or by dietary deficiency. 

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