title: Biosynthetic precursors of the lipase inhibitor lipstatin.
abstract: Three putative intermediates in the biosynthesis of the lipase inhibitor lipstatin were synthesized in stable isotope-labeled form and were added to fermentation cultures of Streptomyces toxytricini. Biosynthetic lipstatin was isolated and analyzed by NMR spectroscopy. [3,10,11,12-(2)H]-(3S,5Z,8Z)-3-hydroxytetradeca-5,8-dienoic acid (9) was shown to serve as a direct biosynthetic precursor of lipstatin. [7,8-(2)H(2)]Hexylmalonate (11) was also incorporated into lipstatin, albeit at a relatively low rate. The leucine moiety of [(13)C-formyl,(15)N]-N-formylleucine (10) was diverted to lipstatin under loss of the (13)C-labeled formyl residue.
authors.affiliation: Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstr. 4, D-85747 Garching, Federal Republic of Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Schuhr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisenreich
authors.forename: Markus
authors.initials: M
authors.lastname: Goese
authors.forename: Peter
authors.initials: P
authors.lastname: Stohler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weber
authors.forename: Ernst
authors.initials: E
authors.lastname: Kupfer
authors.forename: Adelbert
authors.initials: A
authors.lastname: Bacher
mesh_terms: D000818:Animals; D002384:Catalysis; D002855:Chromatography, Thin Layer; D003903:Deuterium; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007930:Leucine / Q000737:chemistry; D008049:Lipase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D000077403:Orlistat; D013302:Streptomyces / Q000378:metabolism*; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; D000077403:Orlistat; C054164:lipstatin; D003903:Deuterium; D008049:Lipase; D007930:Leucine