4
1 Introduction
J. Gomes and A.S. Menawat
Spectinomycin is a broad spectrum antibiotic produced primarily by Abbott
Laboratories and Upjohn Company in the USA. Since the initial isolation of the
antibiotic by researchers from both companies technology has come a long way
to large scale industrial production. We found no literature relating to fundamental research, such as the application of genetic engineering, in improving the
yields of spectinomycin. Most of the existing literature relates to the determination of the structure of spectinomycin and its measurement by various analytical
techniques. Production technology is well established and various improvements have been made from engineering contributions.
This work investigates the relation between glucose and oxygen in spectinomycin bioproduction. Previous research at Abbott indicate that spectinomycin production is favored at two different concentrations of glucose. This
phenomenon is examined in detail and the significance of the results are
discussed.
Following a general overview of antibiotics spectinomycin is discussed in
some detail, including methods of production and analysis. Results of the
experimental optimization of glucose feed concentration and analysis of the
results are presented. The mechanism of spectinomycin biosynthesis is described
by a model employing an exponential structure. We show conclusively that
biosynthesis depends on the allocation of glucose and oxygen resource by the
microorganism and that yield can be controlled by manipulating these two
variables. Finally, nonlinear systems theory is applied to predict the concentration from air flow rate values. A control strategy for optimal spectinomycin
production is also presented.
1.1 Physiology of Antibiotics
Among the diverse secondary metabolites available a group of biologically
active compounds called antibiotics occupy a special status. Since the 1940's,
discoveries of new and potent molecules have contributed significantly to
advances in medicine and agriculture. However, the search continues for new
antibiotics and other secondary metabolites to combat naturally resistant fungi
and bacteria, as well as those microbes which have acquired resistance.
It is remarkable that microorganisms producing antibiotics remain viable in
their own environment. In spite of this apparent insensitivity, addition of
antibiotic to the culture during active growth undermines the viability of the
microorganism. Organisms usually start to produce antibiotics after passing
through the active growth phase. The initiation of antibiotic production varies
from organism to organism and on the environmental conditions. Normally,
enzymes directly involved in the antibiotic production are repressed or inhibited
during the growth phase.
1 Introduction
J. Gomes and A.S. Menawat
Spectinomycin is a broad spectrum antibiotic produced primarily by Abbott
Laboratories and Upjohn Company in the USA. Since the initial isolation of the
antibiotic by researchers from both companies technology has come a long way
to large scale industrial production. We found no literature relating to fundamental research, such as the application of genetic engineering, in improving the
yields of spectinomycin. Most of the existing literature relates to the determination of the structure of spectinomycin and its measurement by various analytical
techniques. Production technology is well established and various improvements have been made from engineering contributions.
This work investigates the relation between glucose and oxygen in spectinomycin bioproduction. Previous research at Abbott indicate that spectinomycin production is favored at two different concentrations of glucose. This
phenomenon is examined in detail and the significance of the results are
discussed.
Following a general overview of antibiotics spectinomycin is discussed in
some detail, including methods of production and analysis. Results of the
experimental optimization of glucose feed concentration and analysis of the
results are presented. The mechanism of spectinomycin biosynthesis is described
by a model employing an exponential structure. We show conclusively that
biosynthesis depends on the allocation of glucose and oxygen resource by the
microorganism and that yield can be controlled by manipulating these two
variables. Finally, nonlinear systems theory is applied to predict the concentration from air flow rate values. A control strategy for optimal spectinomycin
production is also presented.
1.1 Physiology of Antibiotics
Among the diverse secondary metabolites available a group of biologically
active compounds called antibiotics occupy a special status. Since the 1940's,
discoveries of new and potent molecules have contributed significantly to
advances in medicine and agriculture. However, the search continues for new
antibiotics and other secondary metabolites to combat naturally resistant fungi
and bacteria, as well as those microbes which have acquired resistance.
It is remarkable that microorganisms producing antibiotics remain viable in
their own environment. In spite of this apparent insensitivity, addition of
antibiotic to the culture during active growth undermines the viability of the
microorganism. Organisms usually start to produce antibiotics after passing
through the active growth phase. The initiation of antibiotic production varies
from organism to organism and on the environmental conditions. Normally,
enzymes directly involved in the antibiotic production are repressed or inhibited
during the growth phase.