298
which gives their cultures a characteristic soil-like odor. They are nonmotile, nonacid–alcohol-fast, and coagulase positive; reduce nitrates to nitrites; degrade adenine, casein, gelatin hypoxanthine, starch and L-tyrosine; and produce pigments.
12.4.1.1 Antimicrobials from Streptomyces
Streptomyces is a leading producer of biologically active and industrially important
secondary metabolites such as antibiotics, anticancer drugs, herbicides, antihelminthic drugs, vitamins and immune modulators. The period from 1942 to 1960 was
marked by the rapid discovery of antibiotics from Streptomyces. More than 75% of
antibiotics in clinical use today are derived from Streptomyces (Watve et al. 2001).
The history of antibiotic discovery from Streptomyces initiated with the discovery
of streptothricin in 1942. This was followed by the isolation of streptomycin in
1943. In 1949, the first antifungal antibiotic nystatin was discovered from
Streptomyces noursei. As the incidence of antimicrobial resistance has grown in
alarming proportions, the search for novel antibiotics from Streptomyces spp. has
intensified in the recent years. The genomes of many species of Streptomyces have
been completely elucidated in the recent years, starting with S. coelicolor in 2001.
The availability of genome information enables a more rapid and highly targeted
screening for antibiotics.
Aminoglycosides The active structure of aminoglycosides contains one or more
aminated sugars joined by glycosidic linkages to a dibasic cyclitol. Amino glycosides are bactericidal in action and acts mainly by binding to prokaryotic ribosomes,
thereby inhibiting protein biosynthesis. The first amino glycoside antibiotic streptomycin was discovered from soil samples containing S. griseus. Streptomycin was
the first clinically effective drug against tuberculosis. Following streptomycin many
more aminoglycosides were discovered form Streptomyces including neomycin,
kanamycin, tobramycin and paromomycin. Neomycin was first discovered in 1949
from S. fradiae. Neomycin is used in topical preparations like antimicrobial creams
and ointments. Kanamycin is isolated from S. kanamyceticus. Tobramycin is produced by S. tenebrarius. It is used mainly in the treatment of pseudomonas infections and possesses excellent activity against gram-negative bacilli. Paromomycin
was first isolated in the 1950s from S. krestomuceticus.
Tetracyclines and Chloramphenicol In 1948, Benjamin Duggar discovered the first
tetracycline, chlorotetracycline, also known by the trade name Aureomycin, from
S. aureofaciens isolated from soil samples collected from Missouri. In 1950, oxytetracycline was isolated from S. rimosus, and is sold under the trade name Terramycin.
These compounds are very similar in structure and biological activity. Tetracycline
was derived from chlorotetracycline by means of catalytic dehalogenation. Later,
high yielding induced auxotrophs of S. viridifaceans were selected for the production of tetracycline. Tetracyclines are bacteriostatic in action. They bind reversibly
to the prokaryotic 30s ribosome and inhibit protein synthesis. Tetracyclines have a
broad spectrum of activity and are used for treatment of a variety of infections
D. Francis
which gives their cultures a characteristic soil-like odor. They are nonmotile, nonacid–alcohol-fast, and coagulase positive; reduce nitrates to nitrites; degrade adenine, casein, gelatin hypoxanthine, starch and L-tyrosine; and produce pigments.
12.4.1.1 Antimicrobials from Streptomyces
Streptomyces is a leading producer of biologically active and industrially important
secondary metabolites such as antibiotics, anticancer drugs, herbicides, antihelminthic drugs, vitamins and immune modulators. The period from 1942 to 1960 was
marked by the rapid discovery of antibiotics from Streptomyces. More than 75% of
antibiotics in clinical use today are derived from Streptomyces (Watve et al. 2001).
The history of antibiotic discovery from Streptomyces initiated with the discovery
of streptothricin in 1942. This was followed by the isolation of streptomycin in
1943. In 1949, the first antifungal antibiotic nystatin was discovered from
Streptomyces noursei. As the incidence of antimicrobial resistance has grown in
alarming proportions, the search for novel antibiotics from Streptomyces spp. has
intensified in the recent years. The genomes of many species of Streptomyces have
been completely elucidated in the recent years, starting with S. coelicolor in 2001.
The availability of genome information enables a more rapid and highly targeted
screening for antibiotics.
Aminoglycosides The active structure of aminoglycosides contains one or more
aminated sugars joined by glycosidic linkages to a dibasic cyclitol. Amino glycosides are bactericidal in action and acts mainly by binding to prokaryotic ribosomes,
thereby inhibiting protein biosynthesis. The first amino glycoside antibiotic streptomycin was discovered from soil samples containing S. griseus. Streptomycin was
the first clinically effective drug against tuberculosis. Following streptomycin many
more aminoglycosides were discovered form Streptomyces including neomycin,
kanamycin, tobramycin and paromomycin. Neomycin was first discovered in 1949
from S. fradiae. Neomycin is used in topical preparations like antimicrobial creams
and ointments. Kanamycin is isolated from S. kanamyceticus. Tobramycin is produced by S. tenebrarius. It is used mainly in the treatment of pseudomonas infections and possesses excellent activity against gram-negative bacilli. Paromomycin
was first isolated in the 1950s from S. krestomuceticus.
Tetracyclines and Chloramphenicol In 1948, Benjamin Duggar discovered the first
tetracycline, chlorotetracycline, also known by the trade name Aureomycin, from
S. aureofaciens isolated from soil samples collected from Missouri. In 1950, oxytetracycline was isolated from S. rimosus, and is sold under the trade name Terramycin.
These compounds are very similar in structure and biological activity. Tetracycline
was derived from chlorotetracycline by means of catalytic dehalogenation. Later,
high yielding induced auxotrophs of S. viridifaceans were selected for the production of tetracycline. Tetracyclines are bacteriostatic in action. They bind reversibly
to the prokaryotic 30s ribosome and inhibit protein synthesis. Tetracyclines have a
broad spectrum of activity and are used for treatment of a variety of infections
D. Francis