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.
Rauhut
Thomas
T
Lehrstuhl für Genetik, Technische Universität München, Am Hochanger 8, 85350 Freising, Germany.
Spiteller
Peter
P
Eisenreich
Wolfgang
W
Spiteller
Michael
M
Glawischnig
Erich
E
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