Biosynthetic origin of BE-10988 in Streptomyces sp. BA10988.
The biosynthetic origin of the tumor-inhibitory derivative, BE-10988, was studied in Streptomyces sp . BA10988 by retrobiosynthetic NMR analysis using [U-(13)C6]glucose as a precursor. The isotopologue compositions of the indole moieties of BE-10988 and tryptophan were virtually identical. This indicates that tryptophan or a closely related metabolite served as a biosynthetic precursor of BE-10988 in analogy to the biosynthetic pathway of camalexin, a structurally related phytoalexin in Arabidopsis thaliana. Labeling experiments with [U-(13)C8(15)N]indole, L-[ring-(2)H5]tryptophan, or L-[U-(13)C3(15)N]cysteine confirmed this hypothesis. However, transfer of the label from [ring-(2)H5]indole pyruvic acid, but not from the known camalexin precursor, [ring-(2)H5]indole-3-acetaldoxime, showed that plants and bacteria have evolved independent mechanisms of tryptophan modification in the biosynthesis of thiazolylindole derivatives.
Lehrstuhl für Genetik, Technische Universität München, Am Hochanger 8, 85350 Freising, Germany.
Thomas
T
Rauhut
Peter
P
Spiteller
Wolfgang
W
Eisenreich
Michael
M
Spiteller
Erich
E
Glawischnig
D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism*; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
D013844:Thiazoles; C069638:BE 10988; D014364:Tryptophan; D005947:Glucose; D003545:Cysteine