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Vitamin B1 biosynthesis in plants requires the essential iron–sulfur
cluster protein, THIC
====================================================================

1. Maja Raschke,
2. Lukas Bürkle,

3. Nadine Müller,
4. Adriano Nunes-Nesi†,

5. Alisdair R. Fernie†,
6. Duilio Arigoni‡,

7. Nikolaus Amrhein, and
8. Teresa B. Fitzpatrick,§

1. 
ETH Zurich, Institute of Plant Sciences, 8092 Zurich,
Switzerland;

2. 
†Max-Planck-Institute for Molecular Plant Physiology, 14476
Potsdam-Golm, Germany; and

3. 
‡ETH Zurich, Organic Chemistry Laboratory, 8093 Zurich,
Switzerland

1. 
Communicated by Roland Douce, Université de Grenoble, Grenoble,
France, October 12, 2007 (received for review September 4, 2007)

Abstract
--------
Vitamin B1 (thiamin) is an essential compound in all organisms acting
as a cofactor in key metabolic reactions and has furthermore been
implicated in responses to DNA damage and pathogen attack in plants.
Despite the fact that it was discovered almost a century ago and
deficiency is a widespread health problem, much remains to be
deciphered about its biosynthesis. The vitamin is composed of a
thiazole and pyrimidine heterocycle, which can be synthesized by
prokaryotes, fungi, and plants. Plants are the major source of the
vitamin in the human diet, yet little is known about the biosynthesis
of the compound therein. In particular, it has never been verified
whether the pyrimidine heterocycle is derived from purine biosynthesis
through the action of the THIC protein as in bacteria, rather than
vitamin B6 and histidine as demonstrated for fungi. Here, we identify
a homolog of THIC in Arabidopsis and demonstrate its essentiality not
only for vitamin B1 biosynthesis, but also plant viability. This step
takes place in the chloroplast and appears to be regulated at several
levels, including through the presence of a riboswitch in the
3′-untranslated region of THIC. Strong evidence is provided for the
involvement of an iron–sulfur cluster in the remarkable chemical
rearrangement reaction catalyzed by the THIC protein for which there
is no chemical precedent. The results suggest that vitamin B1
biosynthesis in plants is in fact more similar to prokaryotic
counterparts and that the THIC protein is likely to be the key
regulatory protein in the pathway.

metabolites
plant viability

riboswitch
thiamin

Arabidopsis
Footnotes
---------

§To whom correspondence should be addressed. E-mail:
 tfitzpatrick{at}ethz.ch
 

Author contributions: T.B.F. designed research; M.R., L.B., N.M.,
A.N.-N., A.R.F., and T.B.F. performed research; M.R. and T.B.F.
contributed new reagents/analytic tools; M.R., L.B., N.M.,
A.N.-N., A.R.F., D.A., N.A., and T.B.F. analyzed data; and T.B.F.
wrote the paper.
 

The authors declare no conflict of interest.
 

This article contains supporting information online at
www.pnas.org/cgi/content/full/0709597104/DC1.
© 2007 by The National Academy of Sciences of the USA

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This Article

1.  Published online before print November 28, 2007, doi:
  10.1073/pnas.0709597104 PNAS December 4, 2007 vol. 104 no. 49
  19637-19642
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