10
J. Gomes and A.S. Menawat
the unmethylated spectinomycin which when methylated produces spectinomycin.
Spectinomycin is produced by several species 1 of Streptomyces, such as
Streptomycesflavopersicus and Streptomyces spectabilis. They belong to a group
of branching microorganisms called actinomycetes. They are closely related to
the true bacteria but are considered as higher, filamentous bacteria. Actinomycetes occupy a distinct position between the true bacteria and the true fungi.
They thrive on a variety of substrates and produce a wide spectrum of antibiotics.
The Abbott Laboratories [23] and the Upjohn Company [24] pioneered the
research on spectinomycin. It was known as actinospectacin when first discovered in the early sixties. It blocks protein synthesis by selectively inhibiting
initiating ribosomes on bacterial and viral messengers although it fails to block
ribosomes already engaged in chain elongation [25]. A series of preliminary
research projects conducted by Upjohn [26, 27] culminated in establishing the
structure of spectinomycin [28]. Later studies [21] further explained the biosynthesis. In particular, Otsuka et al. [22] studies the stereochemical aspects of
the biosynthesis and explained the mode of conversion of glucose into the
actinamine moiety and the formation of the cyclitol portion.
Cotton seed flour, soybean meal and brewers yeast, which are common
constituents of industrial medium formulations, provide a rich source of amino
acids for the organism. Ammonium hydroxide, the base used to control pH, also
acts as a source of nitrogen during the growth phase. Between the growth phase
(primary metabolism) and the production phase (secondary metabolism), there
is a distinct switch from acidic to basic pH. Hence during the production phase
only sulfuric acid needs to be added in requisite amounts to control the pH,
whereas, during the growth phase only ammonium hydroxide needs to be added
to control pH. Since the microorganism is capable of using amino acids directly
from the medium, active anaploretic pathways must be present. However, it is
the carbon source which plays a decisive role in spectinomycin biosynthesis.
Glucose is the limiting substrate for growth and spectinomycin production by
Streptomyces. Since glucose-6-phosphate is the precursor both for spectinomycin biosynthesis and for growth and proliferation, allocation of this resource
is critical for its production.
2.2 Role of Glucose and Oxygen
Microorganisms producing spectinomycin utilize glucose for growth and maintenance and for the synthesis of the antibiotic. Since spectinomycin is an
aminoglycoside and is synthesized from the intermediate glucose-6-phosphate,
1 The species name will not be disclosed on confidential grounds.
J. Gomes and A.S. Menawat
the unmethylated spectinomycin which when methylated produces spectinomycin.
Spectinomycin is produced by several species 1 of Streptomyces, such as
Streptomycesflavopersicus and Streptomyces spectabilis. They belong to a group
of branching microorganisms called actinomycetes. They are closely related to
the true bacteria but are considered as higher, filamentous bacteria. Actinomycetes occupy a distinct position between the true bacteria and the true fungi.
They thrive on a variety of substrates and produce a wide spectrum of antibiotics.
The Abbott Laboratories [23] and the Upjohn Company [24] pioneered the
research on spectinomycin. It was known as actinospectacin when first discovered in the early sixties. It blocks protein synthesis by selectively inhibiting
initiating ribosomes on bacterial and viral messengers although it fails to block
ribosomes already engaged in chain elongation [25]. A series of preliminary
research projects conducted by Upjohn [26, 27] culminated in establishing the
structure of spectinomycin [28]. Later studies [21] further explained the biosynthesis. In particular, Otsuka et al. [22] studies the stereochemical aspects of
the biosynthesis and explained the mode of conversion of glucose into the
actinamine moiety and the formation of the cyclitol portion.
Cotton seed flour, soybean meal and brewers yeast, which are common
constituents of industrial medium formulations, provide a rich source of amino
acids for the organism. Ammonium hydroxide, the base used to control pH, also
acts as a source of nitrogen during the growth phase. Between the growth phase
(primary metabolism) and the production phase (secondary metabolism), there
is a distinct switch from acidic to basic pH. Hence during the production phase
only sulfuric acid needs to be added in requisite amounts to control the pH,
whereas, during the growth phase only ammonium hydroxide needs to be added
to control pH. Since the microorganism is capable of using amino acids directly
from the medium, active anaploretic pathways must be present. However, it is
the carbon source which plays a decisive role in spectinomycin biosynthesis.
Glucose is the limiting substrate for growth and spectinomycin production by
Streptomyces. Since glucose-6-phosphate is the precursor both for spectinomycin biosynthesis and for growth and proliferation, allocation of this resource
is critical for its production.
2.2 Role of Glucose and Oxygen
Microorganisms producing spectinomycin utilize glucose for growth and maintenance and for the synthesis of the antibiotic. Since spectinomycin is an
aminoglycoside and is synthesized from the intermediate glucose-6-phosphate,
1 The species name will not be disclosed on confidential grounds.