5. ANTIBIOSIS AND ANTIBIOTICS
317
However, Tsukada and co-workers (284), working with Zygosaccharomyces sojae, found that the growth inhibition could not be explained by
the slight depression of respiration and glycolysis observed. They surmised that the antibiotic either uncouples ATP formation or prevents
ATP uptake in the synthesis of protein and nucleic acids.
It has also been advanced that cycloheximide interferes with cell wall
biosynthesis in such a way that an irreversible enlargement of that structure occurs and, as a consequence, formation of giant yeast cells (285).
The activity of cycloheximide on diverse fungi appears to be linked
to their capacity to utilize sugars (286), and its primary action on
many different sensitive cells seems to be the inhibition of DNA synthesis
(286a).
The structural analogy of sarcomycin (XXXV) to antibiotics which
are simple derivatives of amino acids has been stressed above. Sarcomycin, however, is probably acetate derived. Produced by Streptomyces
erythrochromogenes,
this compound, identified as 2-methylene-3-oxocyclopentanecarboxylic acid, shows moderate activity against some
species of gram-positive bacteria and protozoa of the genus Trichomonas. Its main interest resides, however, practically, in its antitumor
effects, and theoretically, in the differences of activity displayed by its
many derivatives. Its hydrogenation yields the 2-methyl derivative, or
dihydrosarcomycin, which has antitumor but no antimicrobial activity.
Heating sarcomycin in vacuo gives a rearrangement product, 2-methyl3-oxocyclopent-l,2-enecarboxylic acid, which is biologically inactive. So
are the high molecular weight polymers that are formed from sarcomycin
in the presence of peroxides. Sarcomycin B, which occurs spontaneously
upon storage of the natural antibiotic at 37°C, is made up of two
molecules of dihydrosarcomycin joined together through their respective
methyl groups and through a 3,2' oxygen bridge. It has some anticancer
but no antimicrobial activity. In the presence of formic acid, sarcomycin
or sarcomycin Β are transformed into sarcomycin E, a compound in
which one molecule of dihydrosarcomycin and one of 2-hydroxydihydrosarcomycin are joined through their methyl groups. This product is antitumoral and antimicrobial. Lyophilization of sarcomycin or sarcomycin
Ε gives a crystalline product, M-crystal, biologically inactive. It differs
from sarcomycin Ε only in that it has lost the 2-hydroxy group and
therefore appears as made up of one molecule of dihydrosarcomycin and
one of sarcomycin rearrangement product linked through their methyl
groups. Treatment of sarcomycin with H 2 S gives the sarcomycins οχ, o 2 ,
and S 3 . In the first and second compounds, the methyl groups of two
molecules of dihydrosarcomycin are joined together, respectively, by a
sulfur and disulfur bridge. The structure of the third one is not known.
317
However, Tsukada and co-workers (284), working with Zygosaccharomyces sojae, found that the growth inhibition could not be explained by
the slight depression of respiration and glycolysis observed. They surmised that the antibiotic either uncouples ATP formation or prevents
ATP uptake in the synthesis of protein and nucleic acids.
It has also been advanced that cycloheximide interferes with cell wall
biosynthesis in such a way that an irreversible enlargement of that structure occurs and, as a consequence, formation of giant yeast cells (285).
The activity of cycloheximide on diverse fungi appears to be linked
to their capacity to utilize sugars (286), and its primary action on
many different sensitive cells seems to be the inhibition of DNA synthesis
(286a).
The structural analogy of sarcomycin (XXXV) to antibiotics which
are simple derivatives of amino acids has been stressed above. Sarcomycin, however, is probably acetate derived. Produced by Streptomyces
erythrochromogenes,
this compound, identified as 2-methylene-3-oxocyclopentanecarboxylic acid, shows moderate activity against some
species of gram-positive bacteria and protozoa of the genus Trichomonas. Its main interest resides, however, practically, in its antitumor
effects, and theoretically, in the differences of activity displayed by its
many derivatives. Its hydrogenation yields the 2-methyl derivative, or
dihydrosarcomycin, which has antitumor but no antimicrobial activity.
Heating sarcomycin in vacuo gives a rearrangement product, 2-methyl3-oxocyclopent-l,2-enecarboxylic acid, which is biologically inactive. So
are the high molecular weight polymers that are formed from sarcomycin
in the presence of peroxides. Sarcomycin B, which occurs spontaneously
upon storage of the natural antibiotic at 37°C, is made up of two
molecules of dihydrosarcomycin joined together through their respective
methyl groups and through a 3,2' oxygen bridge. It has some anticancer
but no antimicrobial activity. In the presence of formic acid, sarcomycin
or sarcomycin Β are transformed into sarcomycin E, a compound in
which one molecule of dihydrosarcomycin and one of 2-hydroxydihydrosarcomycin are joined through their methyl groups. This product is antitumoral and antimicrobial. Lyophilization of sarcomycin or sarcomycin
Ε gives a crystalline product, M-crystal, biologically inactive. It differs
from sarcomycin Ε only in that it has lost the 2-hydroxy group and
therefore appears as made up of one molecule of dihydrosarcomycin and
one of sarcomycin rearrangement product linked through their methyl
groups. Treatment of sarcomycin with H 2 S gives the sarcomycins οχ, o 2 ,
and S 3 . In the first and second compounds, the methyl groups of two
molecules of dihydrosarcomycin are joined together, respectively, by a
sulfur and disulfur bridge. The structure of the third one is not known.