Collie-Birch polyketide hypothesis

This groundbreaking experiment initiated a period of frenetic activity in the natural products community, which established that non-aromatic compounds can likewise be biosynthesized by condensation of esters according to what became known as the Collie-Birch polyketide hypothesis [27, 28). In this regard, impressive radiolabeling studies by Cane established the propionate origin of the carbon framework in erythronolide A, one of the classic macrolide antibiotics (Figure 4.1) [29]. 

In 1907, Collie proposed that polymers of ketene (CH2=C=O) might be precursors of such compounds as orsellinic acid, a common constituent of lichens. The hypothesis was modernized in 1953 by Birch and Donovan, who proposed that several molecules of acetyl-CoA are condensed (Eq. 21-19) but without the two reduction steps required in biosynthesis of fatty acids (Fig. 17-12).329 As we now know they were correct in assuming that the condensation occurs via malonyl-CoA and an acyl carrier group of an enzyme. The resulting p-polyketone can react in various ways to give the large group of compounds known as polyketides. 

Collie s hypothesis that aromatic compounds are made biologically from ethanoic acid was greatly expanded by A. J. Birch to include an extraordinary number of diverse compounds. The generic name acetogenin has been suggested as a convenient classification for ethanoate (acetate)-derived natural products, but the name polyketides also is used. Naturally occurring aromatic compounds and quinones are largely made in this way. An example is 2-hydroxy-6-methylbenzoic acid formed as a metabolite of the mold Penicillium urticae ... 

---