Teicoplanin biosynthesis genes in Actinoplanes teichomyceticus

The genetic determinants for the biosynthesis of the glycopeptide antibioti c teicoplanin were identified. In order to isolate the corresponding gene c luster, oligonucleotides derived from highly conserved motifs in peptide sy nthetases were used. These synthetic probes, and gene fragments derived fro m the balhimycin gene cluster of Amycolatopsis mediterranei, led to the ide ntification of the likely teicoplanin gene cluster centered on a region of ca. 110 kb from the genome of Actinoplanes teichomyceticus, the teicoplanin producer. Partial nucleotide sequences identified partial ORFs likely to e ncode two glycosyltransferases, three P-450 monooxygenases and one ABC tran sporter. The corresponding genes have been found in other glycopeptide gene clusters. Furthermore, upstream to the peptide synthetase region a segment was identified with a remarkable similarity to the vanHAX operon, conferri ng resistance to glycopeptides in enterococci. Thus, in contrast to the oth er glycopeptide producers thus far analyzed, in A. teichomyceticus the gene s for teicoplanin biosynthesis are closely linked to homologs of glycopepti de resistance commonly found in vancomycin-resistant enterococci.