5. ANTIBIOSIS AND ANTIBIOTICS
269
thus preventing the liberation of activated amino acids and their assembly into peptide chains (56a,b,c). Many analogs, with slightly different
activities, have been synthesized, and 3'-amino-3'-deoxyadenosine was
recognized as an antitumor agent in cultures of Helminthosporum sp.
(56d).
The aglycon fraction assumes a greater importance in streptomycete
antibiotics such as amicetin (XV, 56e), its precursor amicetin Β and the
related bamicetin, all from S. plicatus, novobiocin (XVI), from S.
sphaeroides, S. niveus, etc., celesticetin I (XVII), from S. caelestis, and
racemomycin Ο (XVIII). The antibiotic action of novobiocin
(57a,b),
analogs of which have been prepared biosynthetically (57c), has been
explained either by its ability to uncouple the phosphorylations (58) or
by its inhibitory effect upon cell wall biosynthesis, in a manner generally
similar to that of the penicillins (59) or D-cycloserine (60), with leakage
of cell constituents (61). More recently, its ability to complex magnesium
ions has been regarded as its fundamental mechanism of action (62).
In a number of antibiotics produced by streptomycetes, sugars are
associated to a polycyclic moiety. Thus, D-fucose and D-digitalose (XIX)
are found in chartreusin (62a). Rhodosamine (XX) is present in ηpyrromycin, rhodomycins A and B, isorhodomycins A and B. An eightcarbon atom amino sugar, resembling mycaminose (XXI, 62b,c,d) and
amosamine (see XV), is found in aklavin and three as yet unidentified
sugars are present in each of the cinerubins A and B, two being common
to both whereas the third is characteristic of the particular antibiotic.
Unusual sugars are also important components of the macrolide antibiotics typically produced by streptomycetes. With the possible exceptions of lylosin and lankamycin, their presence in the molecule appears
to be necessary for antibiotic activity.
Mycaminose (XXI) is a component of the newly described antibiotic
acumycin, which, produced by Streptomyces griseoflavus, very likely
belongs in the macrolide group (62e).
Mycaminose and mycarose (XXII, 62f,g) are found together in
carbomycins A and Β and in tylosin. The latter sugar is associated with
2,3,4,6-tetradeoxy-4-dimethylaminohexopyranose (XXIII) and a third
sugar in the foromacidins or spiramycins. Desosamine (62h,i,j) or picrocin (XXIV) is found in picromycin, methymycin, neomethymycin, and
narbomycin. It is also present, together with cladinose (XXV), in erythromycins A and B, with an unidentified sugar, C 7 Hi 3 0 3 , in erythromycin C, with L-oleandrose (XXVI) in oleandomycin. The last-cited sugar
is also a component of the steroid glycoside oleandrin, which is found
in the leaves of Nerium oleander.
269
thus preventing the liberation of activated amino acids and their assembly into peptide chains (56a,b,c). Many analogs, with slightly different
activities, have been synthesized, and 3'-amino-3'-deoxyadenosine was
recognized as an antitumor agent in cultures of Helminthosporum sp.
(56d).
The aglycon fraction assumes a greater importance in streptomycete
antibiotics such as amicetin (XV, 56e), its precursor amicetin Β and the
related bamicetin, all from S. plicatus, novobiocin (XVI), from S.
sphaeroides, S. niveus, etc., celesticetin I (XVII), from S. caelestis, and
racemomycin Ο (XVIII). The antibiotic action of novobiocin
(57a,b),
analogs of which have been prepared biosynthetically (57c), has been
explained either by its ability to uncouple the phosphorylations (58) or
by its inhibitory effect upon cell wall biosynthesis, in a manner generally
similar to that of the penicillins (59) or D-cycloserine (60), with leakage
of cell constituents (61). More recently, its ability to complex magnesium
ions has been regarded as its fundamental mechanism of action (62).
In a number of antibiotics produced by streptomycetes, sugars are
associated to a polycyclic moiety. Thus, D-fucose and D-digitalose (XIX)
are found in chartreusin (62a). Rhodosamine (XX) is present in ηpyrromycin, rhodomycins A and B, isorhodomycins A and B. An eightcarbon atom amino sugar, resembling mycaminose (XXI, 62b,c,d) and
amosamine (see XV), is found in aklavin and three as yet unidentified
sugars are present in each of the cinerubins A and B, two being common
to both whereas the third is characteristic of the particular antibiotic.
Unusual sugars are also important components of the macrolide antibiotics typically produced by streptomycetes. With the possible exceptions of lylosin and lankamycin, their presence in the molecule appears
to be necessary for antibiotic activity.
Mycaminose (XXI) is a component of the newly described antibiotic
acumycin, which, produced by Streptomyces griseoflavus, very likely
belongs in the macrolide group (62e).
Mycaminose and mycarose (XXII, 62f,g) are found together in
carbomycins A and Β and in tylosin. The latter sugar is associated with
2,3,4,6-tetradeoxy-4-dimethylaminohexopyranose (XXIII) and a third
sugar in the foromacidins or spiramycins. Desosamine (62h,i,j) or picrocin (XXIV) is found in picromycin, methymycin, neomethymycin, and
narbomycin. It is also present, together with cladinose (XXV), in erythromycins A and B, with an unidentified sugar, C 7 Hi 3 0 3 , in erythromycin C, with L-oleandrose (XXVI) in oleandomycin. The last-cited sugar
is also a component of the steroid glycoside oleandrin, which is found
in the leaves of Nerium oleander.