Enzyme inducer

^[1]An enzyme inducer is a type of drug that increases the metabolic activity of an enzyme either by binding to the enzyme and activating it, or by increasing the expression of the gene coding for the enzyme.

Classic examples: barbiturates (phenobarbitone), antiepileptics and rifampin. Carbamazepine is another enzyme inducer. By enzyme induction it can reduce efficacy of haloperidol and oral contraceptives.

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 al., 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 ana- logues, 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 al. (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 pro- duced. 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 f3-mannosidase which will convert mannosi- dostreptomycin to streptomycin. It is now possible to produce a number of heterolo- gous proteins in yeasts, fungi and bacteria. These in- clude proteins of viral, human, animal, plant and mi-crobial ongm (Peberdy, 1988; Wayne Davies, 1991). However, heterologous proteins may show some degree of toxicity to the host and have a major influence on the stability of heterologous protein expression. As well as restricting cell growth as biomass the toxicity will provide selective conditions for segregant cells which no longer synthesize the protein at such a high level (Goodey et al., 1987). Therefore, optimum growth con- ditions may be achieved by not synthesizing a heterolo- gous protein continuously and only inducing it after the host culture has grown up in a vessel to produce sufficient biomass (Piper and Kirk, 1991). In cells of S. cerevisiae where the Gall promoter is part of the gene expression system, product formation may be induced by galactose addition to the growth medium which contains glycerol or low non-repressing levels of glu- cose as a carbon source. One commercial system that has been developed is based on the alcA promoter in Aspergillus nidulans to express human interferon a 2 (Wayne Davies, 1991). This can be induced by volatile chemicals, such as ethylmethyl ketone, which are added when biomass has increase to an adequate level and the growth medium contains a non-repressing carbon source or low non-re- pressing levels of glucose. Methylotrophic yeasts such as Hansenula polymor- pha and Pichia pastoris may be used as alternative systems because of the presence of an alcohol oxidase promoter (Veale and Sudbery, 1991). During growth on methanol, which also acts as an inducer, the promoter is induced to produce about 30% of the cell protein. In the presence of glucose or ethanol it is undetectable. Expression systems have been developed with P. pas- toris for tumour necrosis factor, hepatitis B surface antigen and a-galactosidase. Hepatitis B surface anti- gen and other heterologous proteins can also be ex- pressed by H. polymorpha.

See also

• Enzyme activator
• Enzyme inhibitor
• Regulation of gene expression
• Enzyme inducers
• Quinoline,carbamazepine

References

• hepatic enzyme inducers
• hepatic enzyme inhibitors