Rauhut Thomas, Spiteller Peter, Eisenreich Wolfgang, Spiteller Michael, Glawischnig Erich
Lehrstuhl für Genetik, Technische Universität München, Am Hochanger 8, 85350 Freising, Germany.
J Org Chem. 2008 Jul 18;73(14):5279-86. doi: 10.1021/jo800375u. Epub 2008 Jun 17.
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.
利用[U-(13)C6]葡萄糖作为前体，通过逆生物合成核磁共振分析，在链霉菌属BA10988中研究了肿瘤抑制衍生物BE-10988的生物合成起源。BE-10988和色氨酸吲哚部分的同位素异构体组成几乎相同。这表明色氨酸或一种密切相关的代谢物作为BE-10988的生物合成前体，类似于拟南芥中结构相关的植物抗毒素camalexin的生物合成途径。用[U-(13)C8(15)N]吲哚、L-[环-(2)H5]色氨酸或L-[U-(13)C3(15)N]半胱氨酸进行的标记实验证实了这一假设。然而，[环-(2)H5]吲哚丙酮酸中的标记转移，而非已知的camalexin前体[环-(2)H5]吲哚-3-乙醛肟中的标记转移，表明植物和细菌在噻唑基吲哚衍生物的生物合成中进化出了独立的色氨酸修饰机制。
