Metabolite analogues General discussion

The antimetabolites discussed so far are close structural analogues of the corresponding metabolites, having generally similar size and shape, and differing... 

There are many examples of polyketide metabolites where the common acetate starter unit is replaced by other groups, and a general discussion of these is outside the scope of this review. Numerous studies have been carried out on the use of analogues of the normal biosynthetic precursors to produce novel structures. This type of precursor-directed biosynthesis has been the subject of a recent comprehensive review [60]. 

Metabolites from cyanobacteria are generally of amino acid or polyketide origin and frequently show potent biological activity. The series of dolastatin metabolites, exemplified by dolastatin-10 (Structure 2.18), are linear peptides which show potent cytotoxic activity and are of clinical interest as anti-tumour agents. Originally isolated in very low yield from the Indian Ocean sea hare Dolabella auricularia, dolastatins are now known to be cyanobacterial products.43,44 The discovery of a microbial source for these pharmaceutically important compounds will facilitate study of their biosynthesis and could potentially lead to the production of structural analogues by provision of modified biosynthetic precursors to the cultivar. As discussed below and in Section VI, toxic secondary metabolites from cyanobacteria have often been implicated in the chemical defenses of sea hares.45"17... 

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