BIOSYNTHESIS OF POLYENE ANTIBIOTICS

A feature of actinomycelates biosynthesis is the incorporation of the intact carbon skeleton of glucose into secondary metabolites. It appears that myco-samine is derived from D-glucose and is Incorporated into the polyene molecule unchanged [95-97,99]. 

The shikimate pathway is the major route to aromatic compounds in actinomycetales. Biosynthesis of the aromatic side chains of candicidin [95] and peri-mycin [100] has been shown to arise directly from glucose via shikimate andp-aminobenzoate. 

In 1958 two important observations were made which proved fundamental to the understanding of the mechanism of action of polyene antibiotics. It was 

Several excellent reviews have described in detail the role of sterols in the mechanism of action of polyenes [103-105]. Only a summary of the evidence will be given. 

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Regulation of secondary metabolites by glucose or ocher easily assimilated carbon sources (glucose repression) occurs in the biosynthesis of several antibiotics (penicillin, aciinomycin, streptomycin, siomycin, bacitracin, etc.) (fora review, see Refs. 89 and 90), but not in the biosynthesis of polyene antibiotics, because glucose is required for their biosynthesis. 

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