Mother Nature's Laboratory
The interconversion of similar chemical species by biological enzymes is nature's way of obtaining chemical diversity. In this way, caffeine can be obtained from AMP (adenosine monophosphate) and GMP (guanosine monophosphate), both of which are based on the purine molecule.
Metabolic pathway of the biosynthesis of caffeine from purine nucleotides in Coffea arabica
The conversion from xanthosine to caffeine occurs in four steps, three of which are methylations. There is a great deal of methylating going on in nature, controlled by a group of enzymes called methyltransferases. As a result, nature also has a highly advanced methylating agent, called S-adenosyl methionine, or SAM.
For example, let us consider the methylation of theobromine to form caffeine in the coffee plant. The formation of SAM occurs by the reaction of the amino acid methionine with a molecule of ATP (adenosine triphosphate), with the displacement of the triphosphates (shown in blue).
The reaction works well for three reasons: sulphur is a good soft nucleophile, triphosphate is a good leaving group, and substitution at a primary carbon is easy.
SAM is a sulphonium salt. Nucleophilic attack on the methyl is the most favoured, and it is in this way that the theobromine is methylated. As always in biochemistry, regioselectivity is dictated by the enzyme which brings the molecules together in the correct orientation for N-methylation. However, this position can be seen to be favourable anyway, as it preserves the aromaticity of the ring and the amide functionality.
where Ad stands for adenosine and R represents the rest of the methionine molecule
Quite clearly, nature is the better chemist.
In the 3.7 billion years since the first organisms turned water and carbon
dioxide into 'organic matter', nature has evolved to conduct the most amazing
reactions that we in the labs can only dream about. But let us not underestimate
our advances; the first 'organic' synthesis only took place in 1828 with
the synthesis of the simple molecule urea, so all our achievements in organic
chemistry, which have been considerable, have occurred within the
last two hundred years. And who knows how many of these advances were fueled
by the consumption of caffeine..?
Metabolic Pathway Diagram adapted
from Biological Sciences Review, Vol.10, No.2, November 1997, p.41
Reaction Schemes adapted from Organic Chemistry, Clayden, Greeves, Warren and Wothers, OUP, 2001
Images used with permission from the following sources:
ATP molecule www.bris.ac.uk/Depts/Chemistry/MOTM/atp/atp1.htm
Images used without permission from
the following sources:
Methionine molecule http://www.chemie.fu-berlin.de/chemistry/bio/aminoacid/met_en.html
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