5. ANTIBIOSIS AND ANTIBIOTICS
303
1. Fatty Acids and Denvatives in Antibiotics
Fatty acids, especially the unsaturated ones, have been reported as
having antimicrobial properties (259) often ascribed to their lowering
effect on surface tension. It is also worth while to recall that one of the
first chemically defined substance isolated from a bacterial culture
(Bacillus mesentericus) with a view to explaining its bactericidal and
bacteriolytic activities was isovaleric acid (260a).
Many of the simpler aliphatic acids found in antibiotics are members
of, or readily derived from, the citric acid cycle or related metabolic
pathways. Longer-chain acids and derivatives are generally synthesized
from acetate through a well-known route involving the participation of
acetyl and malonyl units, coenzyme A, and biotin.
Actinomycin J 2 (or B), from Streptomyces antibioticus, was identified
as the dodecyl ester of 5-oxostearic acid. Isovaleric acid, linked to the
sugar mycarose (XXII), is found in carbomycins A and Β (CXIV).
The occurrence of a fatty, or hydroxy fatty, acid moiety in glycolipid
(V, VI), polypeptide (Table III, viscosine, LVI-LVIII), and depsipeptide (LXIII-LXX) antibiotics has been reported above. Similar moieties
are also found in simpler substances partially derived from amino acids:
fumarylylalanine, serratamic acid, antibiotics of the holothin-pyrrothin
group (XLV), pyo compounds, cephalosporins Ν (XXXVIIb) and C
(XXXVIII). The α-aminoadipoyl and acetoxy groups of the latter were
shown, by isotope studies, to be acetate derived
(260b).
A number of microorganisms are endowed with the ability to produce special types of acids, many of them antibiotic, as a result of the
condensation of keto acids with long-chain fatty acids. Examples are
roccellic (260c) (XCII), rangiformic (XCIII), and caperatic (XCIV)
CH 3
— (CH 2 ) n — CH—COOH
CH—COOH
CH 3
— (CH 2 ) 13 CH—COOH
CH—COOH
CH 3
H—CH—COOH
Roccellic acid
(XCII)
Rangiformic acid
(XCin)
CH 3
— (CH 2 ) 13 - CH- COOH
CH 3 —(CH 2 ) 15 — CH— COOH
HO—C COOH
CH—COOH
H—CH-COOH
HO—CH—COOH
Caperatic acid
(XCIV)
Ungulinic acid
(XCV)
303
1. Fatty Acids and Denvatives in Antibiotics
Fatty acids, especially the unsaturated ones, have been reported as
having antimicrobial properties (259) often ascribed to their lowering
effect on surface tension. It is also worth while to recall that one of the
first chemically defined substance isolated from a bacterial culture
(Bacillus mesentericus) with a view to explaining its bactericidal and
bacteriolytic activities was isovaleric acid (260a).
Many of the simpler aliphatic acids found in antibiotics are members
of, or readily derived from, the citric acid cycle or related metabolic
pathways. Longer-chain acids and derivatives are generally synthesized
from acetate through a well-known route involving the participation of
acetyl and malonyl units, coenzyme A, and biotin.
Actinomycin J 2 (or B), from Streptomyces antibioticus, was identified
as the dodecyl ester of 5-oxostearic acid. Isovaleric acid, linked to the
sugar mycarose (XXII), is found in carbomycins A and Β (CXIV).
The occurrence of a fatty, or hydroxy fatty, acid moiety in glycolipid
(V, VI), polypeptide (Table III, viscosine, LVI-LVIII), and depsipeptide (LXIII-LXX) antibiotics has been reported above. Similar moieties
are also found in simpler substances partially derived from amino acids:
fumarylylalanine, serratamic acid, antibiotics of the holothin-pyrrothin
group (XLV), pyo compounds, cephalosporins Ν (XXXVIIb) and C
(XXXVIII). The α-aminoadipoyl and acetoxy groups of the latter were
shown, by isotope studies, to be acetate derived
(260b).
A number of microorganisms are endowed with the ability to produce special types of acids, many of them antibiotic, as a result of the
condensation of keto acids with long-chain fatty acids. Examples are
roccellic (260c) (XCII), rangiformic (XCIII), and caperatic (XCIV)
CH 3
— (CH 2 ) n — CH—COOH
CH—COOH
CH 3
— (CH 2 ) 13 CH—COOH
CH—COOH
CH 3
H—CH—COOH
Roccellic acid
(XCII)
Rangiformic acid
(XCin)
CH 3
— (CH 2 ) 13 - CH- COOH
CH 3 —(CH 2 ) 15 — CH— COOH
HO—C COOH
CH—COOH
H—CH-COOH
HO—CH—COOH
Caperatic acid
(XCIV)
Ungulinic acid
(XCV)