7 MethyLxanthosine synthase

Caffeine (Fig. 11.3), widely used by humans as a stimulatory drug, has so far been detected only in a few plant species. The biological roles of caffeine are believed to be in defense against herbivory or as an allelopathic response to potential competitors.83 Caffeine is derived from the purine alkaloid xanthosine. From xanthosine, three methylations are necessary to produce caffeine. First, xanthosine is methylated on N7 by 7-methylxanthosine synthase (MXS or 7NMT) to produce 7-methylxanthosine, which is enzymatically hydrolyzed to produce 7-methylxanthine and ribose.85,86 The methylations of N1 and N3 of 7-methylxanthine to produce 1,3,7-trimethylxanthine (caffeine) occur in young leaves of tea, and the same enzyme, caffeine synthase, apparently catalyzes both reactions.55 In coffee plants, caffeine is mainly found in the beans but also occurs in the leaves. Caffeine is stored in the vacuoles of coffee leaves as a complex with polyphenols such as chlorogenic acid.87 In contrast to tea, coffee plants appear to have separate enzymes for each step of N-methylation.57... 

Figure 4 Caffeine biosynthesis. XMT, xanthosine N-methyltransferase (also called 7-methylxanthosine synthase) XN, methyixanthosine nucleotidase MXMT, 7-methylxanthine-N-methyltransferase (also called theobromine synthase) DXMT, dimethyIxanthine-N-methyltransferase (also called caffeine synthase).

Mizuno K, Kato M, Irino F, Yoneyama N, Fujimura T, Ashihara H. The first committed step reaction of caffeine biosynthesis 7-methylxanthosine synthase is closely homologous to caffeine synthase in coffee. FEES Lett. 2003 547 56-60. 

Fig. 8.8 Biosynthetic pathway for tropane and purine alkaloids, (a) Tiopane alkaloid ODC ornithine decarboxylase, PMT putrescine Ai-methyltransferase). (b) Purine alkaloid XMT xanthosine W-methyltransferase/7-methylxanthosine synthase, XN 7-methylxanthosine nucleotidase, MXMT 7-methylxanthine Ai-methyltransferase/theobromine synthase, DXMT dimethyl-xanthine Ai-methyltransferase/caffeine synthase) (Adopted from Ref. [15])...

Fig. 29.1 The biosynthetic pathways of caffeine from xanthosine. The major pathway that consists of four steps is shown with solid arrows. Conversion of 7-methylxanthosine to 7-methylxanthine is catalyzed by nucleosidase activity involved in 7-methylxanthosme synthase or a specific Af-methyl nncleosidase. Minor pathways, shown with dotted arrows, are theoretically possible. They may occur because of the broad substrate specificity of caffeine synthase or other Ai-methyltransferases. Enzymes 7mXS 7-methylxanthosine synthase, CS caffeine synthase, TS theobromine synthase, SAM 5-adenosyl-L-methionine, SAH S-adenosyl-L-homocysteine...

A-Methyl-mitomycin, 984 A-Methylmitomycin A, 984 Methyl orange, 1063 JV-Methylpelletierine, 305, 306, 337 2-Methyl-2-pentanal, 2887 1 -Methy 1-4-phenyl-1,2,3,6-tetrahydropyridme (MPTP), 3699, 3710, 3718 iV-Methyl porfiromycin, 983, 984 Methylpseudoephedrine, 1219 A-Methylputrescine oxidase, 182 Methylpyrazines, 1610 Methylscutelloside, 3051 Methyltransferase, 1655, 1670 A-Methyltryptamine, 540 Methyluric acids, 954, 956,961 Methylxanthines, 954, 1178, 1180, 1182 7-Methylxanthosine synthase, 959 Metopolophium dirrhodum, 4094 Metrodorea, H6... 

The biosynthesis of caffeine begins with the methylation of xanthosine to yield N-methylxanthosine by the enzyme xanthosine N-methyltransferase (XMT) (also called 7-methy-Ixanthosine synthase) (171-173). N-methylxanthosine is converted to N-methylxanthine by methylxanthine nucleosidase, an enzyme that has not been cloned yet (174). N-methylxanthine is converted to theobromine by 7-methylxanthine-N-methyl-transferase (MXMT) (also called theobromine synthase), a second N-methyltransferase (171, 175). Theobromine is converted to caffeine by a final N-methyltransferase, dimethylxanthine-N-methyltransferase (DXMT) (also called caffeine synthase) (171). 

Figure 4.12 Biosynthesis of purine aikaioids. Enzyme abbreviations CS, caffeine synthase MXN, 7-methylxanthosine nucieosidase MXS, 7-methyixanthosine synthase.

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