title: Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii.
abstract: Vicenistatin, an antitumor antibiotic isolated from Streptomyces halstedii, is a unique 20-membered macrocyclic lactam with a novel aminosugar vicenisamine. The vicenistatin biosynthetic gene cluster (vin) spanning approximately 64 kbp was cloned and sequenced. The cluster contains putative genes for the aglycon biosynthesis including four modular polyketide synthases (PKSs), glutamate mutase, acyl CoA-ligase, and AMP-ligase. Also found in the cluster are genes of NDP-hexose 4,6-dehydratase and aminotransferase for vicenisamine biosynthesis. For the functional confirmation of the cluster, a putative glycosyltransferase gene product, VinC, was heterologously expressed, and the vicenisamine transfer reaction to the aglycon was chemically proved. A unique feature of the vicenistatin PKS is that the loading module contains only an acyl carrier protein domain, in contrast to other known PKS-loading modules containing certain activation domains. Activation of the starter acyl group by separate polypeptides is postulated as well.
authors.affiliation: Department of Chemistry, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Kinya
authors.initials: K
authors.lastname: Katayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Minami
authors.forename: Miyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Eguchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kakinuma
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D005809:Genes, Regulator; D019751:Intramolecular Transferases / Q000378:metabolism; D007769:Lactams / Q000737:chemistry / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000378:metabolism; D005810:Multigene Family; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D007769:Lactams; D018942:Macrolides; D009097:Multienzyme Complexes; C082785:vicenistatin; D019751:Intramolecular Transferases; C021570:methylaspartate mutase; D008025:Ligases