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Koffler et al. (1947)

Griseofulvin

Zn

Grove (1967)

ments of biological interest (Atomic numbers 23-30, 42). Of these nine, the concentrations of manganese, iron and zinc are the most critical in secondary metabolism. In every secondary metabolic system in which sufficient data has been reported, the yield of the product varies linearly with the logarithmic concentration of the 'key' metal. The linear relationship does not apply at concentrations of the metal which are either insufficient, or toxic, to cell growth. Some of the primary and secondary microbial products whose yields are affected by concentrations of trace metals greater than those required for maximum growth are given in Table 4.11.

Chlorine does not appear to play a nutritional role in the metabolism of fungi (Foster, 1949). It is, however, required by some of the halophilic bacteria (Lar-sen, 1962). Obviously, in those fermentations where a chlorine-containing metabolite is to be produced the synthesis will have to be directed to ensure that the non-chloro-derivative is not formed. The most important compounds are chlortetracycline and griseofulvin. In griseofulvin production, adequate available chloride is provided by the inclusion of at least 0.1% KCI (Rhodes et al., 1955), as well as the chloride provided by the complex organic materials included as nitrogen sources. Other chlorine containing metabolites are caldriomycin, nornidulin and mollisin.

Chelators

Many media cannot be prepared or autoclaved without the formation of a visible precipitate of insoluble or sterols. Many of the natural carbon and nitrogen sources used in media formulations contain all or some of the required growth factors (Atkinson and Mavituna, 1991a). When there is a vitamin deficiency it can often be eliminated by careful blending of materials (Rhodes and Fletcher, 1966). It is important to remember that if only one vitamin is required it may be occasionally more economical to add the pure vitamin, instead of using a larger bulk of a cheaper multiple vitamin source. Calcium pantothenate has been used in one medium formulation for vinegar production (Beaman, 1967). In processes used for the production of glutamic acid, limited concentrations of biotin must be present in the medium (see Chapter 3). Some production strains may also require thiamine (Kinoshita and Tanaka, 1972).

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