Genes for polyketide secondary metabolic pathways in microorganisms and plants.

Abstract

Recent advances in molecular genetics have led to the isolation, sequencing and functional analysis of genes encoding synthases that catalyse the formation of several classes of polyketides. The structures of the genes and their protein products differ strikingly in the various examples. For Streptomyces aromatic polyketides, exemplified by granaticin and tetracenomycin, the synthases correspond to Type II (bacterial and plant) fatty acid synthases in consisting of distinct proteins for such processes as condensation, acyl carrier function and ketoreduction. In contrast, for actinomycete macrolides such as erythromycin, similar catalytic functions are performed by a set of multifunctional proteins resembling Type I (animal) fatty acid synthases, but with every step in chain-building being catalysed by a different enzymic domain. Penicillium patulum has a simple Type I synthase for 6-methylsalicylic acid. For plant chalcones and stilbenes, a single small polypeptide acts as a condensing enzyme for carbon chain-building and may be unrelated to any of the other polyketide and fatty acid synthases. Thus, although these systems share a common general mechanism of chain assembly, they must differ in the ways that synthase 'programming' has evolved to determine chain length, choice of chain starter and extender units, and handling of successive keto groups during chain assembly, and so control the great diversity of possible chemical products.