Biosynthesis of lipstatin. Incorporation of multiply deuterium-labeled (5Z,8Z)-tetradeca-5,8-dienoic acid and octanoic acid.
Fermentation experiments with Streptomyces toxytricini were performed using (5Z,8Z)-[10,11,12,12-(2)H]tetradeca-5,8-dienoic acid or a mixture of [2,2-(2)H(2)]- and [8,8,8-(2)H(3)]octanoic acid as supplements. (2)H NMR and mass spectroscopy confirmed the incorporation of (5Z,8Z)-[10,11,12,12-(2)H]tetradeca-5,8-dienoic acid into the C(13) side chain as well as into the C(6) side chain of lipstatin. Moreover, deuterium was incorporated into the C(6) side chain of lipstatin from the 8-position but not from the 2-position of octanoate. The data establish that the beta-lactone moiety of lipstatin is formed by condensation of a C(8) and a C(14) fatty acid with a concomitant exchange of the H-2 atoms of the C(8) fatty acid.
Goese
M
M
Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstr. 4, D-85747 Garching, Federal Republic of Germany.
Eisenreich
W
W
Kupfer
E
E
Stohler
P
P
Weber
W
W
Leuenberger
H G
HG
Bacher
A
A
D002210:Caprylates / Q000378:metabolism*; D003903:Deuterium; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005285:Fermentation; D007783:Lactones / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013302:Streptomyces / Q000378:metabolism*
D002210:Caprylates; D005231:Fatty Acids, Unsaturated; D007783:Lactones; C108157:5,8-tetradecadienoic acid; C054164:lipstatin; D003903:Deuterium; C031492:octanoic acid