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* Yields are not so high as by other techniques

* Yields are not so high as by other techniques no longer available for re-oxidation of NADH2, its place as hydrogen acceptor is taken by dihydroacetone phosphate, produced during glycolysis. The product of this reaction is glycerol-3-phosphate, which is converted to glycerol.

The application of general and specific inhibitors are illustrated in Table 4.13. In most cases the inhibitor is effective in increasing the yield of the desired product and reducing the yield of undesirable related products. A number of studies have been made with potential chlorination inhibitors, e.g. bromide, to minimize chlortetracycline production during a tetracycline fermentation (Gourevitch et al., 1956; Lepetit S.p.A., 1957; Goodman et al, 1959; Lein et al., 1959; Szumski, 1959).

Inhibitors have also been used to affect cell-wall structure and increase the permeability for release of metabolites. The best example is the use of penicllin and surfactants in glutamic acid production (Phillips and Somerson, 1960).

Inducers

The majority of enzymes which are of industrial interest are inducible. Induced enzymes are synthesized only in response to the presence in the environment of an inducer. Inducers are often substrates such as starch or dextrins for amylases, maltose for pullulanase and pectin for pectinases. Some inducers are very potent, such as isovaleronitrile inducing nitralase (Kobayashi et ah, 1992). Substrate analogues that are not attacked by the enzyme may also serve as enzyme inducers. Most inducers which are included in microbial enzyme media (Table 4.14) are substrates or substrate analogues, but intermediates and products may sometimes be used as inducers. For example, maltodextrins will induce amylase and fatty acids induce lipase. However, the cost may prohibit their use as inducers in a commercial process. Reviews have been published by Aunstrup et ah (1979) and Demain (1990).

One unusual application of an inducer is the use of yeast mannan in streptomycin production (Inamine et al, 1969). During the fermentation varying amounts of streptomycin and mannosidostreptomycin are produced. Since mannosidostreptomycin has only 20% of the biological activity of streptomycin, the former is an undesirable product. The production organism Strep-tomyces griseus can be induced by yeast mannan to produce /3-mannosidase which will convert mannosidostreptomycin to streptomycin.

It is now possible to produce a number of heterologous proteins in yeasts, fungi and bacteria. These include proteins of viral, human, animal, plant and mi-

Table 4.13. Specific and general inhibitors used in fermentations

Product

Inhibitor

Main effect

Micro-organism

Reference

Glycerol

Sodium bisulphite

Acetaldehyde pro

Saccharomyces

Eoff et al.

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