8
J. Gomes and A.S. Menawat
Intracellular ATP levels affect the production of antibiotic. Martin and
Demain [15] observed that extracellular phosphate concentration directly affected the intraceullar concentration of ATP. They observed that Streptomyces
9riseus synthesized antibiotic only under phosphate limited conditions. Phosphate addition increased the concentration of phosphoribosyl pyrophosphate
which stimulates the uptake of adenine.
Biosynthetic mechanisms for growth are directly related to the available
energy and hence the intracellular ATP concentration. The correlation between
ATP concentration or adenylate charge in cells and regulatory enzymes is still
controversial. Energy charge defined by Atkinson and Walton [16] as
ATP + 0.5ADP
ATP + ADP + AMP
provides a measure for the amount of energy stored in the adenylate system.
During the exponential growth phase of Escherichia coli the energy charge
varies between 0.8-0.9 [17]. The microorganism remains viable for energy
charge values between 0.8-0.85. For energy charge values below 0.5 the cells die.
These values are true for most microorganisms [18]. Energy charge numbers
and their correlation with antibiotic production are still not universally accepted [19]. Martin et al. [20] established that at an energy charge of about 0.8,
Streptomyees 9riseus produces antibiotic. Their studies show that an addition of
10 mM phosphate increases the energy charge number to 0.85 with a simultaneous switch to active growth. Although the energy charge number increases
only by 0.5, the intracellular ATP concentration triples. Clearly, both extracellular and intracellular phosphate strongly regulate antibiotic biosynthesis.
In the case of spectinomycin it is not phosphorus or nitrogen but carbon
which regulates its biosynthesis. It has been established conclusively [21,22]
that the ultimate precursor for the two carbon rings of spectinomycin is glucose.
Therefore, production of spectinomycin begins with limiting levels of glucose in
the medium.
2 Spectinomycin Biosynthesis
2.1 Organism and Metabolism
Spectinomycin is a broad spectrum antibiotic used primarily for the treatment
of penicillin resistant gonorrhea. The antibiotic is an aminoglycoside comprising
two glucose moieties joined together by two oxygen bridges in a tri-ring
structure (Fig. 1). The formation of the aminoglycoside group of antibiotics
triggers off directly from glucose-6-phosphate, i.e., intracellular glucose. Two
possible pathways exist for the production of spectinomycin from intracellular
glucose: (i) by aldolase conversion to myo-inositol and (ii) by oxidoreductase
J. Gomes and A.S. Menawat
Intracellular ATP levels affect the production of antibiotic. Martin and
Demain [15] observed that extracellular phosphate concentration directly affected the intraceullar concentration of ATP. They observed that Streptomyces
9riseus synthesized antibiotic only under phosphate limited conditions. Phosphate addition increased the concentration of phosphoribosyl pyrophosphate
which stimulates the uptake of adenine.
Biosynthetic mechanisms for growth are directly related to the available
energy and hence the intracellular ATP concentration. The correlation between
ATP concentration or adenylate charge in cells and regulatory enzymes is still
controversial. Energy charge defined by Atkinson and Walton [16] as
ATP + 0.5ADP
ATP + ADP + AMP
provides a measure for the amount of energy stored in the adenylate system.
During the exponential growth phase of Escherichia coli the energy charge
varies between 0.8-0.9 [17]. The microorganism remains viable for energy
charge values between 0.8-0.85. For energy charge values below 0.5 the cells die.
These values are true for most microorganisms [18]. Energy charge numbers
and their correlation with antibiotic production are still not universally accepted [19]. Martin et al. [20] established that at an energy charge of about 0.8,
Streptomyees 9riseus produces antibiotic. Their studies show that an addition of
10 mM phosphate increases the energy charge number to 0.85 with a simultaneous switch to active growth. Although the energy charge number increases
only by 0.5, the intracellular ATP concentration triples. Clearly, both extracellular and intracellular phosphate strongly regulate antibiotic biosynthesis.
In the case of spectinomycin it is not phosphorus or nitrogen but carbon
which regulates its biosynthesis. It has been established conclusively [21,22]
that the ultimate precursor for the two carbon rings of spectinomycin is glucose.
Therefore, production of spectinomycin begins with limiting levels of glucose in
the medium.
2 Spectinomycin Biosynthesis
2.1 Organism and Metabolism
Spectinomycin is a broad spectrum antibiotic used primarily for the treatment
of penicillin resistant gonorrhea. The antibiotic is an aminoglycoside comprising
two glucose moieties joined together by two oxygen bridges in a tri-ring
structure (Fig. 1). The formation of the aminoglycoside group of antibiotics
triggers off directly from glucose-6-phosphate, i.e., intracellular glucose. Two
possible pathways exist for the production of spectinomycin from intracellular
glucose: (i) by aldolase conversion to myo-inositol and (ii) by oxidoreductase