Biosynthetic precursors of the lipase inhibitor lipstatin.
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.
Schuhr
Christoph A
CA
Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstr. 4, D-85747 Garching, Federal Republic of Germany.
Eisenreich
Wolfgang
W
Goese
Markus
M
Stohler
Peter
P
Weber
Wolfgang
W
Kupfer
Ernst
E
Bacher
Adelbert
A
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
D004791:Enzyme Inhibitors; D007783:Lactones; D000077403:Orlistat; C054164:lipstatin; D003903:Deuterium; D008049:Lipase; D007930:Leucine