title: A gene cluster for prenylated naphthoquinone and prenylated phenazine biosynthesis in Streptomyces cinnamonensis DSM 1042.
abstract: Streptomyces cinnamonensis DSM 1042 produces two classes of secondary metabolites of mixed isoprenoid/nonisoprenoid origin: the polyketide-isoprenoid compound furanonaphthoquinone I (FNQ I) and several prenylated phenazines, predominantly endophenazine A. We now report the cloning and sequence analysis of a 55 kb gene cluster required for the biosynthesis of these compounds. Several inactivation experiments confirmed the involvement of this gene cluster in the biosynthesis of FNQ I and endophenazine A. The six identified genes for endophenazine biosynthesis showed close similarity to phenazine biosynthetic genes from Pseudomonas. Of the 28 open reading frames identified in the adjacent FNQ I cluster, 13 showed close similarity to genes contained in the cluster for furaquinocin-a structurally similar metabolite from another Streptomyces strain. These genes included a type III polyketide synthase sequence, a momA-like monooxygenase gene, and two cloQ-like prenyltransferase genes designated fnq26 and fnq28. Inactivation experiments confirmed the involvement of fnq26 in FNQ I biosynthesis, whereas no change in secondary-metabolite formation was observed after fnq28 inactivation. The FNQ I cluster contains a contiguous group of five genes, which together encode all the enzymatic functions required for the recycling of S-adenosylhomocysteine (SAH) to S-adenosylmethionine (SAM). Two SAM-dependent methyltransferases are encoded within the cluster. Inactivation experiments showed that fnq9 is responsible for the 7-O-methylation and fnq27 for the 6-C-methylation reaction in FNQ I biosynthesis.
authors.affiliation: Eberhard-Karls-Universität Tübingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Haagen
authors.forename: Kerstin
authors.initials: K
authors.lastname: Glück
authors.forename: Katja
authors.initials: K
authors.lastname: Fay
authors.forename: Bernd
authors.initials: B
authors.lastname: Kammerer
authors.forename: Bertolt
authors.initials: B
authors.lastname: Gust
authors.forename: Lutz
authors.initials: L
authors.lastname: Heide
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D008954:Models, Biological; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation; D009285:Naphthoquinones / Q000378:metabolism*; D010619:Phenazines / Q000378:metabolism*; D017368:Protein Prenylation / Q000235:genetics; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*
chemical_list: D009285:Naphthoquinones; D010619:Phenazines; C469530:endophenazine A