5. ANTIBIOSIS AND ANTIBIOTICS
315
It is worth noting that biologically inactive metabolites with a
macrolide structure are also found in streptomycete cultures: an interesting example is given by the macrotetrolides (CXIX) nonactin (275a),
monactin, dinactin, and trinactin (275b).
The structure of the rifamycins, a group of antibiotics comprising
natural substances produced by Streptomyces mediterranei (275c) and
semisynthetic derivatives (275d), was recently elucidated (275e). The
structural formula of rifamycin Β (CXIXb) shows that antibiotics of
this family are macrocyclic lactones. However, in contradistinction to
the other macrolides, they have a dibenzene nucleus and they contain no
sugars nor sugar derivatives.
It is generally assumed that the lactone moiety of the macrolides
is acetate derived. However, isotope studies have shown that, for
erythromycin (276, 277) and methymycin, it is formed from propionate,
in the latter case with the possible incorporation of one acetate fragment.
At least part of carbomycin also appears to be propionate derived
(278a,b).
The biogenesis, in most instances, is visualized as the result of a
series of alternate oxidations on a single methylated straight-chain precursor (CXV-CXVIII), although in a few cases (see arrows in CXIII,
CXIV), the possible coupling of two or three smaller precursor units has
been suggested.
Various metabolic disturbances have been reported in bacteria submitted to the action of nonpolyene macrolides. Their fundamental mode
of action remains, however, unknown.
5. Alicyclic Antibiotics
It was demonstrated that the shikimic acid pathway does not play
any part in the biosynthesis of palitantin (CV), which is wholly acetate
derived. A similar mode of formation is also likely for the nitrogen-free
moiety of cycloheximide (279a) or actidione (CXX), from Streptomyces
griseus, S. noursei, S. albulus, and a Streptomyces related to S. viridochromogenes or S. olivochromogenes. This antifungal, antiprotozoal, and
antialgal (279b) antibiotic, which has the unexpected property of being
very repellent to rats, is but one member of a family of closely related
metabolites featuring a substituted cyclohexyl linked to glutarimide
through an ethyl chain. Two of its possible isomers (279c) are known
to occur in nature: naramycin B, from Streptomyces sp., and a diastereoisomer produced by S. albulus. They have very little antifungal activity.
The streptovitacins, from S. griseus, mainly known as anticancer agents,
are cycloheximides monohydroxylated, respectively, at position 5 (A),
4 (B), or 3 (C 2 ). They have some antifungal activity. The 5-acetoxy
315
It is worth noting that biologically inactive metabolites with a
macrolide structure are also found in streptomycete cultures: an interesting example is given by the macrotetrolides (CXIX) nonactin (275a),
monactin, dinactin, and trinactin (275b).
The structure of the rifamycins, a group of antibiotics comprising
natural substances produced by Streptomyces mediterranei (275c) and
semisynthetic derivatives (275d), was recently elucidated (275e). The
structural formula of rifamycin Β (CXIXb) shows that antibiotics of
this family are macrocyclic lactones. However, in contradistinction to
the other macrolides, they have a dibenzene nucleus and they contain no
sugars nor sugar derivatives.
It is generally assumed that the lactone moiety of the macrolides
is acetate derived. However, isotope studies have shown that, for
erythromycin (276, 277) and methymycin, it is formed from propionate,
in the latter case with the possible incorporation of one acetate fragment.
At least part of carbomycin also appears to be propionate derived
(278a,b).
The biogenesis, in most instances, is visualized as the result of a
series of alternate oxidations on a single methylated straight-chain precursor (CXV-CXVIII), although in a few cases (see arrows in CXIII,
CXIV), the possible coupling of two or three smaller precursor units has
been suggested.
Various metabolic disturbances have been reported in bacteria submitted to the action of nonpolyene macrolides. Their fundamental mode
of action remains, however, unknown.
5. Alicyclic Antibiotics
It was demonstrated that the shikimic acid pathway does not play
any part in the biosynthesis of palitantin (CV), which is wholly acetate
derived. A similar mode of formation is also likely for the nitrogen-free
moiety of cycloheximide (279a) or actidione (CXX), from Streptomyces
griseus, S. noursei, S. albulus, and a Streptomyces related to S. viridochromogenes or S. olivochromogenes. This antifungal, antiprotozoal, and
antialgal (279b) antibiotic, which has the unexpected property of being
very repellent to rats, is but one member of a family of closely related
metabolites featuring a substituted cyclohexyl linked to glutarimide
through an ethyl chain. Two of its possible isomers (279c) are known
to occur in nature: naramycin B, from Streptomyces sp., and a diastereoisomer produced by S. albulus. They have very little antifungal activity.
The streptovitacins, from S. griseus, mainly known as anticancer agents,
are cycloheximides monohydroxylated, respectively, at position 5 (A),
4 (B), or 3 (C 2 ). They have some antifungal activity. The 5-acetoxy