Biosynthesis of Tetrahydrofolate
STEREOCHEMISTRY OF DIHYDRONEOPTERIN ALDOLASE*
Victoria
Illarionova
,
Wolfgang
Eisenreich§,
Markus
Fischer,
Christoph
Haußmann¶,
Werner
Römisch,
Gerald
Richter
, and
Adelbert
Bacher
From the Lehrstuhl für Organische Chemie und Biochemie,
Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany
7,8-Dihydroneopterin aldolase catalyzes the
formation of the tetrahydrofolate precursor,
6-hydroxymethyl-7,8-dihydropterin, and is a potential target for
antimicrobial and anti-parasite chemotherapy. The last step of the
enzyme-catalyzed reaction is believed to involve the protonation of an
enol type intermediate. In order to study the stereochemical course of
that reaction step, [1',2',3',6,7-13C5]dihydroneopterin was
treated with aldolase in deuterated buffer. The resulting, partially
deuterated
[6
,6,7-13C3]6-hydroxymethyl-7,8-dihydropterin
was converted to partially deuterated
6-(R)-[6,7,9,11-13C4]5,10-methylenetetrahydropteroate
by a sequence of three enzyme-catalyzed reactions followed by treatment
with [13C]formaldehyde. The product was analyzed by
multinuclear NMR spectroscopy. The data show that the carbinol group of
enzymatically formed 6-hydroxymethyl-dihydropterin contained
2H predominantly in the pro-S position.
*
This work was supported by the Deutsche
Forschungsgemeinschaft, the Fonds der Chemischen Industrie, the
Hans-Fischer-Gesellschaft, and by EC Grant FMRX-CT980204.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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