- Characterization of the: N -methyltransferases involved in the biosynthesis of toxoflavin, fervenulin and reumycin from Streptomyces hiroshimensis ATCC53615
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Toxoflavin (1), fervenulin (2), and reumycin (3), known to be produced by plant pathogen Burkholderia glumae BGR1, are structurally related 7-azapteridine antibiotics. Previous biosynthetic studies revealed that N-methyltransferase ToxA from B. glumae BGR1 catalyzed the sequential methylation at N6 and N1 in pyrimido[5,4-e]-as-triazine-5,7(6H,8H)-dione (4) to generate 1. However, the N8 methylation of 4 in the biosynthesis of fervenulin remains unclear. To explore the N-methyltransferases required for the biosynthesis of 1 and 2, we identified and characterized the fervenulin and toxoflavin biosynthetic gene clusters in S. hiroshimensis ATCC53615. On the basis of the structures of intermediates accumulated from the four N-methyltransferase gene inactivation mutants and systematic enzymatic methylation reactions, the tailoring steps for the methylation order in the biosynthesis of 1 and 2 were proposed. The N-methylation order and routes for the biosynthesis of fervenulin and toxoflavin in S. hiroshimensis are more complex and represent an obvious departure from those in B. glumae BGR1.
- Su, Can,Yan, Yijun,Guo, Xiaowei,Luo, Jianying,Liu, Chongxi,Zhang, Zhouxin,Xiang, Wen-Sheng,Huang, Sheng-Xiong
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supporting information
p. 477 - 481
(2019/01/24)
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- Pyrimidines. XXXIII [1]. Synthesis and properties of new fervenulin derivatives
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A series of new 3-substituted fervenulin (6,8-dimethylpyrimido[5,4-e]-1,2,4-triazine-5,7-dione) (1) derivatives have been synthesized by modifying the 3-alkyl- and aralkyl side-chains. Brominations of 3-methyl-15, 3-ethyl-16- and 3-benzylfervenulin (17) l
- Werner-Simon, Susanne,Pfleiderer, Wolfgang
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p. 949 - 960
(2007/10/03)
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- PURINES, PYRIMIDINES, AND CONDENSED SYSTEMS BASED ON THEM. 6. REACTIVITY OF 7- AND 9-AMINOXANTHINES TOWARD OXIDIZING AGENTS AND SOME ELECTROPHILES. SYNTHESIS OF THE ANTIBIOTICS FERVENULIN AND RHEUMYCIN
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The action of various oxidizing agents on 7- and 9-aminotheophyllines and also on 1-methyl-9-aminoxanthine was studied. 7-Aminotheophyllines are oxidized by almost all the oxidizing agents to 6,8-dimethylpyrimido-as-triazine-5,7(6H,8H)-dione (40-90 percent). 1-Methyl-9-aminoxanthine and 9-aminotheophylline are oxidized with greater difficulty.The best results are obtained with hydrogen peroxide, which transforms these amines with yields of ca. 40 percent into the antibiotics rheumycin and fervenulin, respectively.Under certain conditions the action of bromine and nitric acid leads to the bromination and nitration of the N-aminoxanthines at position 8.A series of the physicochemical characteristics of the N-aminoxanthines were investigated.The factors which affect their behavior toward oxidizing agents and electrophiles are discussed.
- Gulevskaya, A. V.,Kuz'menko, V. V.,Pozharskii, A. F.,Kuz'menko, T.A.,Shorshnev, S. V.,et al.
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