1887

Abstract

Medermycin is a aromatic -glycoside antibiotic classified in the benzoisochromanequinones (BIQs), which presents several interesting biosynthetic problems concerning polyketide synthase (PKS), post-PKS tailoring and deoxysugar pathways. The biosynthetic gene cluster for medermycin (the cluster) was cloned from sp. AM-7161. Completeness of the clone was proved by the heterologous expression of a cosmid carrying the entire cluster in CH999 to produce medermycin. The DNA sequence of the cosmid (36 202 bp) revealed 34 complete ORFs, with an incomplete ORF at either end. Functional assignment of the deduced products was made for PKS and biosynthetically related enzymes, tailoring steps including strereochemical control, oxidation, angolosamine pathway, -glycosylation, and regulation. The cluster was estimated to be about 30 kb long, covering 29 ORFs. An unusual characteristic of the cluster is the disconnected organization of the minimal PKS genes: -ORF23 encoding the acyl carrier protein is 20 kb apart from -ORF1 and -ORF2 for the two ketosynthase components. Secondly, the six genes (-ORF14, 15, 16, 17, 18 and 20) for the biosynthesis of the deoxysugar, angolosamine, are all contiguous. Finally, the finding of a glycosyltransferase gene, -ORF8, suggests a possible involvement of conventional -glycosylation in medermycin biosynthesis. Comparison among the three complete BIQ gene clusters – and those for actinorhodin () and granaticin () – revealed some common genes whose deduced functions are unavailable from database searches (the ‘unknowns’). An example is -ORF5, a homologue of -ORF3 and -ORF18, which was highlighted by a recent proteomic analysis of A3(2).

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2003-07-01
2019-11-19
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