title: Genome-based discovery of a novel membrane-bound 1,6-dihydroxyphenazine prenyltransferase from a marine actinomycete.
abstract: Recently, novel prenylated derivatives of 1,6-dihydroxyphenazine have been isolated from the marine sponge-associated Streptomyces sp. SpC080624SC-11. Genome sequencing of this strain now revealed a gene cluster containing all genes necessary for the synthesis of the phenazine and the isoprenoid moieties. Unexpectedly, however, the cluster did not contain a gene with similarity to previously investigated phenazine prenyltransferases, but instead a gene with modest similarity to the membrane-bound prenyltransferases of ubiquinone and menaquinone biosynthesis. Expression of this gene in E. coli and isolation of the membrane fraction proved that the encoded enzyme, Mpz10, catalyzes two successive prenylations of 1,6-dihydroxyphenazine. Mpz10 is the first example of a membrane-bound enzyme catalyzing the prenylation of a phenazine substrate, and one of few examples of membrane-bound enzymes involved in the prenylation of aromatic secondary metabolites in microorganisms.
authors.affiliation: Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zeyhle
authors.affiliation: Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Bauer
authors.affiliation: Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Kalinowski
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.affiliation: Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gross
authors.affiliation: Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Heide
mesh_terms: D039903:Actinobacteria / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D016680:Genome, Bacterial; D007700:Kinetics; D013058:Mass Spectrometry; D005810:Multigene Family; D010619:Phenazines / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D054876:Prenylation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity
chemical_list: D010619:Phenazines; D011994:Recombinant Proteins; D004122:Dimethylallyltranstransferase