title: Harnessing the synthetic capabilities of glycopeptide antibiotic tailoring enzymes: characterization of the UK-68,597 biosynthetic cluster.
abstract: In this study, a draft genome sequence of Actinoplanes sp. ATCC 53533 was assembled, and an 81-kb biosynthetic cluster for the unusual sulfated glycopeptide UK-68,597 was identified. Glycopeptide antibiotics are important in the treatment of infections caused by Gram-positive bacteria. Glycopeptides contain heptapeptide backbones that are modified by many tailoring enzymes, including glycosyltransferases, sulfotransferases, methyltransferases, and halogenases, generating extensive chemical and functional diversity. Several tailoring enzymes in the cluster were examined in vitro for their ability to modify glycopeptides, resulting in the synthesis of novel molecules. Tailoring enzymes were also expressed in the producer of the glycopeptide aglycone A47934, generating additional chemical diversity. This work characterizes the biosynthetic program of UK-68,597 and demonstrates the capacity to expand glycopeptide chemical diversity by harnessing the unique chemistry of tailoring enzymes.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, The M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8N 3Z5 (Canada).
authors.forename: Grace
authors.initials: G
authors.lastname: Yim
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kalan
authors.forename: Kalinka
authors.initials: K
authors.lastname: Koteva
authors.forename: Maulik N
authors.initials: MN
authors.lastname: Thaker
authors.forename: Nicholas
authors.initials: N
authors.lastname: Waglechner
authors.forename: Irene
authors.initials: I
authors.lastname: Tang
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D053898:Biosynthetic Pathways / Q000235:genetics*; D006020:Glycopeptides / Q000096:biosynthesis* / Q000737:chemistry; D008848:Micromonosporaceae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008968:Molecular Conformation; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D014166:Transferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D010088:Oxidoreductases; D014166:Transferases
keywords: antibiotics; biosynthesis; glycopeptides; natural products; synthetic biology