6
J. Gomes and A.S. Menawat
pathway of the antibiotic, before production begins. These critical enzymes
become active at low nutritional levels only under growth limiting conditions.
This clearly suggests that catabolite repression is one of the mechanisms of
regulation. However it is still not known whether repression occurs at the
transcription or at the translation level.
1.1.1 Carbon Regulation
Glucose, an excellent carbon source for growth, interferes with the biosynthesis
of many antibiotics. In antibiotic production facilities where glucose and a more
slowly metabolizable carbon source (citrate, glycerol) is used, glucose is consumed during growth while the second carbon source is utilized for antibiotic
production. Depending on the microorganism, the carbon regulation may be
triggered by a carbon source other than glucose. For example, Streptomyces
niveus prefers citrate as the carbon source over glucose in the synthesis of
novobiocin [10].
Often the specific growth rate determines the onset of antibiotic synthesis. In
such situations, controlling the growth rate in the optimum ranges for either
growth or production eliminates the interference from glucose. For example,
maintaining the growth rate within the range of 0.009 and 0.014 h- 1, prevents
the decay of penicillin [11, 12]. The residual glucose concentration also affects
the commencement of secondary metabolism in the fungal culture. Consequently, the feeding rate of glucose determines the productivity of penicillin by
Penicillium chrysogenum. Martin and Demain [1] have presented a detailed
study of the interfering effects of glucose and other carbon sources on various
antibiotic synthetic processes.
1.1.2 Nitrogen Regulation
Nitrogen atoms constitute an important part of many antibiotic molecules and
cellular materials and therefore participates in important regulatory mechanisms. Usually, microorganisms integrate nitrogen containing primary metabolites into the final antibiotic molecule. Nitrogen regulates the production of
proteins and other nitrogenous biomolecules by microorganisms. It also regulates the activity of enzymes which utilize nitrogen resources. For example,
ammonia represses nitrite and nitrate reductase, glutamate dehydrogenase and
extracellular protease. Microorganisms also show distinct preference for the
type of nitrogen nutrient they need for growth or synthesis of secondary
metabolites.
The literature provides sufficient evidence that nitrogen significantly influences the production of antibiotics. Streptomyces griseus produced the highest titer
of Streptomycin when the media contained soya bean meal, a rich source of
nitrogen [13]. Novobiocin production by Streptomyces niveus requires proline
J. Gomes and A.S. Menawat
pathway of the antibiotic, before production begins. These critical enzymes
become active at low nutritional levels only under growth limiting conditions.
This clearly suggests that catabolite repression is one of the mechanisms of
regulation. However it is still not known whether repression occurs at the
transcription or at the translation level.
1.1.1 Carbon Regulation
Glucose, an excellent carbon source for growth, interferes with the biosynthesis
of many antibiotics. In antibiotic production facilities where glucose and a more
slowly metabolizable carbon source (citrate, glycerol) is used, glucose is consumed during growth while the second carbon source is utilized for antibiotic
production. Depending on the microorganism, the carbon regulation may be
triggered by a carbon source other than glucose. For example, Streptomyces
niveus prefers citrate as the carbon source over glucose in the synthesis of
novobiocin [10].
Often the specific growth rate determines the onset of antibiotic synthesis. In
such situations, controlling the growth rate in the optimum ranges for either
growth or production eliminates the interference from glucose. For example,
maintaining the growth rate within the range of 0.009 and 0.014 h- 1, prevents
the decay of penicillin [11, 12]. The residual glucose concentration also affects
the commencement of secondary metabolism in the fungal culture. Consequently, the feeding rate of glucose determines the productivity of penicillin by
Penicillium chrysogenum. Martin and Demain [1] have presented a detailed
study of the interfering effects of glucose and other carbon sources on various
antibiotic synthetic processes.
1.1.2 Nitrogen Regulation
Nitrogen atoms constitute an important part of many antibiotic molecules and
cellular materials and therefore participates in important regulatory mechanisms. Usually, microorganisms integrate nitrogen containing primary metabolites into the final antibiotic molecule. Nitrogen regulates the production of
proteins and other nitrogenous biomolecules by microorganisms. It also regulates the activity of enzymes which utilize nitrogen resources. For example,
ammonia represses nitrite and nitrate reductase, glutamate dehydrogenase and
extracellular protease. Microorganisms also show distinct preference for the
type of nitrogen nutrient they need for growth or synthesis of secondary
metabolites.
The literature provides sufficient evidence that nitrogen significantly influences the production of antibiotics. Streptomyces griseus produced the highest titer
of Streptomycin when the media contained soya bean meal, a rich source of
nitrogen [13]. Novobiocin production by Streptomyces niveus requires proline