Actinomycete Antibiotics

Erythronolide, the macrocyclic lactone which is the aglycon of the complex antibiotic erythromycin (Fig. l), represents a perfect example of a branched chain lipid entirely made up of repeating 3 carbon subunits (2). Although, quantitatively, branched chain fatty acids are not important lipid constituents, ~.~g.~a~e-~el~-rttecte~i~--v~~~in~n~~nn~s-in--~-wid~-vasiety. of natural products. Methymycin (3), neomethymycin (4), oleandomycin (5), pikromycin (6, 7), and other antibiotics of the macrolide group contain aglycons which are partially branched lactones similar to erythronolide. Mycolipenic and mycoceranic acids, present in large amounts in the lipids of tubercule bacilli (8, 9), are partially branched fatty acids again with the same type of repeating 3 carbon subunit. Other substances which may be considered to have at least one 3 carbon subunit are odd numbered straight chain fatty acids and a wide variety of fatty acids and other substances found to have one or more C-methyl group (cf. 10). Robinson has proposed that 3 carbon subunits like those in mycolipenic and mycoceranic acids could arise from propionate or its “biological equivalent” (11). Evidence exists which indicates that this concept may be true for some of the simpler fatty acids which contain 3 carbon units. For instance, n-valeric acid formed in the sheep rumen (12) or by Clostridium kluyveti (13) seems to be derived from propionate and acetate as does the @hydroxyvaleric acid produced by mouse liver slices (14). The perfused cow udder also incorporates propionate-l-Cl* extensively into the odd numbered and branched fatty acids of the milk fats (15). Of more relevance to the 3 carbon units in erythronolide is the recent observation that a-methylbutyric acid, formed by isolated muscle of Ascwis lumbricoides, is made from acetate and propionate with the branch methyl group arising from C-3 of the propionate and the carboxyl group coming from C-l (16).