Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus

Abstract

The glycopeptide teicoplanin is used for the treatment of serious infections caused by Gram-positive pathogens. The tcp gene cluster, devoted to teicoplanin biosynthesis in the actinomycete Actinoplanes teichomyceticus, was isolated and characterized. From sequence analysis, the tcp cluster spans approximately 73 kb and includes 39 ORFs participating in teicoplanin biosynthesis, regulation, resistance and export. Of these, 34 ORFs find a match in at least one of the five glycopeptide gene clusters previously characterized. Putative roles could be assigned for most of the tcp genes. The two glycosyltransferases responsible for attaching amino sugars to amino acids 4 and 6 of the teicoplanin aglycon were overexpressed in Escherichia coli and characterized. They both recognize N-acetylglucosamine as the substrate. tGtfA can add a sugar residue in the presence or absence of N-acetylglucosamine at amino acid 4, while tGtfB can only glycosylate the teicoplanin aglycon.

Diversity of nonribosomal peptide synthetase and polyketide synthase genes in the genus Actinoplanes found in Mongolia

“…6,7,21 To our knowledge, this is the first report focused on the genus Actinoplanes and the results obtained here strongly supported the conclusion that the secondary metabolite gene variety observed here in the genus Actinoplanes was comparable to those of the genome-sequenced genus. This is because most Actinoplanes strains analyzed here contained novel and diverse NRPS or PKS genes or both.…”

Phosphate-Controlled Regulator for the Biosynthesis of the Dalbavancin Precursor A40926

“…Specifically, the cluster encodes the putative regulators Dbv3 (LuxR-like) and Dbv4 (StrR-like), as well as the putative response regulator Dbv6 and the sensor-kinase Dbv22, that may be part of a two-component system. Sequence information is also available for five other gene clusters devoted to glycopeptides, namely, chloroeremomycin (cep) (44), balhimycin (bal) (24,27), complestatin (com) (6), A47934 (sta) (26), and teicoplanin (tcp) (18,34). All clusters contain an strR-like regulator.…”

NovG, a DNA-binding protein acting as a positive regulator of novobiocin biosynthesis

“…The function of the small ORF cloY remains to be elucidated. Genes with obvious similarity to cloY have been found in many other clusters, such as those for coumermycin A 1 , teicoplanin (Sosio et al, 2004), complestatin (Chiu et al, 2001), CDA (Hojati et al, 2002) and balhimycin (Pelzer et al, 1999), but not in the novobiocin cluster.…”

“…One of these families comprises the strR-like genes and includes, besides novG, cloG and couG, also dbv4 of the glycopeptide antibiotic A40926 (Sosio et al, 2003), bbr of the balhimycin (Pelzer et al, 1999) and tcp28 of the teicoplanin (Sosio et al, 2004) clusters. Another family comprises the SARPs, i.e.…”