naphthoquinones and naphterpin

Topics: Biological Products; Catalysis; Crystallography; Dimethylallyltranstransferase; Flavonoids; Macrolides; Mevalonic Acid; Multigene Family; Naphthoquinones; Plants; Prenylation; Protein Folding; Streptomyces; Substrate Specificity; Terpenes

A concise and divergent strategy for the synthesis of the naphterpin and marinone meroterpenoid families has been developed. The approach features a succession of pericyclic reactions-an aromatic Claisen rearrangement, a retro-6π-electrocyclization, and two Diels-Alder reactions-which facilitated the first total synthesis of naphterpin itself in five steps from 2,5-dimethoxyphenol, alongside similar syntheses of 7-demethylnaphterpin and debromomarinone. Late-stage oxidation and bromination reactions were also investigated, leading to the first total syntheses of naphterpins B and C and isomarinone.

Topics: Biological Products; Molecular Structure; Naphthoquinones; Stereoisomerism

A member of the marine streptomycete clade MAR4,

Topics: Aquatic Organisms; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Naphthoquinones; Spectrophotometry, Ultraviolet; Streptomyces; Terpenes

The anti-oxidant naphterpin is a natural product containing a polyketide-based aromatic core with an attached 10-carbon geranyl group derived from isoprenoid (terpene) metabolism. Hybrid natural products such as naphterpin that contain 5-carbon (dimethylallyl), 10-carbon (geranyl) or 15-carbon (farnesyl) isoprenoid chains possess biological activities distinct from their non-prenylated aromatic precursors. These hybrid natural products represent new anti-microbial, anti-oxidant, anti-inflammatory, anti-viral and anti-cancer compounds. A small number of aromatic prenyltransferases (PTases) responsible for prenyl group attachment have only recently been isolated and characterized. Here we report the gene identification, biochemical characterization and high-resolution X-ray crystal structures of an architecturally novel aromatic PTase, Orf2 from Streptomyces sp. strain CL190, with substrates and substrate analogues bound. In vivo, Orf2 attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during naphterpin biosynthesis. In vitro, Orf2 catalyses carbon-carbon-based and carbon-oxygen-based prenylation of a diverse collection of hydroxyl-containing aromatic acceptors of synthetic, microbial and plant origin. These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases.

Topics: Antioxidants; Biological Products; Cloning, Molecular; Crystallography, X-Ray; Dimethylallyltranstransferase; Genes, Bacterial; Magnesium; Models, Molecular; Molecular Structure; Naphthoquinones; Open Reading Frames; Protein Conformation; Streptomyces; Substrate Specificity

Topics: Animals; Antioxidants; Chromatography, Thin Layer; Free Radical Scavengers; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Microsomes, Liver; Molecular Conformation; Molecular Structure; Naphthoquinones; Rats; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Streptomyces

Topics: Antioxidants; Computers; Fermentation; Molecular Structure; Naphthoquinones; Streptomyces; X-Ray Diffraction