Abstract
Many important antibiotics such as tetracyclines, erythromycin, adriamycin, monensin, rifamycin and avermectins are polyketides. In their biosynthesis, multifunctional synthases1 catalyse iterated condensation of thio-esters derived from acetate, propionate or butyrate to yield aliphatic chains of varying length and carrying different alkyl substituents. Subsequent modifications, including aromatic or macrolide ring closure or specific methylations or glycosylations, generate further chemical diversity. It has been suggested that, if different polyketide synthases had a common evolutionary origin, cloned DNA coding for one synthase might be used as a hybridization probe for the isolation of others2. We show here that this is indeed possible. Study of a range of such synthase genes and their products should help to elucidate what determines the choice and order of condensation of different residues in polyketide assembly, and might yield, by in vitro recombination or mutagenesis, synthase genes capable of producing novel antibiotics3. Moreover, because genes for entire antibiotic pathways are usually clustered in Streptomyces4, cloned polyketide synthase genes are valuable in giving access to groups of linked biosynthetic genes.
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Malpartida, F., Hallam, S., Kieser, H. et al. Homology between Streptomyces genes coding for synthesis of different polyketides used to clone antibiotic biosynthetic genes. Nature 325, 818–821 (1987). https://doi.org/10.1038/325818a0
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DOI: https://doi.org/10.1038/325818a0
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