title: The first prenylation step in hyperforin biosynthesis.
abstract: Prenylation reactions contribute considerably to the diversity of natural products. Polyprenylated secondary metabolites include hyperforin which is both quantitatively and pharmacologically a major constituent of the medicinal plant Hypericum perforatum (St. John's wort). Cell cultures of the related species Hypericum calycinum were found to contain a prenyltransferase activity which is likely to catalyze the first prenylation step in hyperforin biosynthesis. The enzyme was soluble and dependent on a divalent cation, with Fe2+ leading to maximum activity (Km=3.8 mM). The preferred prenyl donor was DMAPP (Km=0.46 mM) and the preferred prenyl acceptor was phlorisobutyrophenone (Km=0.52 mM). A broad pH optimum from 6.5 to 8.5 and a temperature optimum from 35 to 40 degrees C were observed. The formation of hyperforins in H. calycinum cell cultures was preceded by an increase in dimethylallyltransferase activity, with the maximum specific activity being 3.6 microkat/kg protein.
authors.affiliation: Institut fuer Pharmazeutische Biologie, Technische Universitaet Braunschweig, Mendelssohnstr. 1, D-38106 Braunschweig, Germany.
authors.forename: Zakia
authors.initials: Z
authors.lastname: Boubakir
authors.forename: Till
authors.initials: T
authors.lastname: Beuerle
authors.forename: Benye
authors.initials: B
authors.lastname: Liu
authors.forename: Ludger
authors.initials: L
authors.lastname: Beerhues
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism*; D004122:Dimethylallyltranstransferase / Q000302:isolation & purification / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D020902:Hypericum / Q000737:chemistry / Q000201:enzymology*; D007501:Iron; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D017368:Protein Prenylation; D012995:Solubility; D013379:Substrate Specificity; D013696:Temperature; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001643:Bridged Bicyclo Compounds; D013729:Terpenes; C423123:adhyperforin; D010696:Phloroglucinol; D007501:Iron; D004122:Dimethylallyltranstransferase; C001654:hyperforin