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Defining vitamin B1 and B6 metabolism in plants: synthesis, regulation and transport

English title Defining vitamin B1 and B6 metabolism in plants: synthesis, regulation and transport
Applicant Fitzpatrick Teresa
Number 119186
Funding scheme SNSF Professorships
Research institution Département de Biologie Végétale Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Biochemistry
Start/End 01.05.2008 - 31.10.2012
Approved amount 950'665.00
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All Disciplines (6)

Discipline
Biochemistry
Botany
Biochemistry
Molecular Biology
Genetics
Cellular Biology, Cytology

Keywords (7)

vitamin metabolism; antioxidant; Arabidopsis thali; B vitamins; metabolism; plants; stress response

Lay Summary (English)

Lead
Lay summary
Vitamins are defined as organic micronutrients that must be obtained in the human diet and are essential compounds for the survival of all organisms. Plants are critical sources of these compounds. However, despite this recognition, the importance of these compounds to plants themselves has been somewhat overlooked. Thus, in most cases the physiological, biochemical and molecular mechanisms that contribute to their synthesis, transport and accumulation in plants are not known. This is especially the case for the water-soluble B vitamins. The main focus of the proposed research will be on vitamin B1 (thiamin) and vitamin B6 (pyridoxine). The essentiality of these compounds to all organisms is recognized by their well-established function as coenzymes for numerous metabolic enzymes. Vitamin B1 is necessary for the catalytic activity of enzymes of primary metabolism. Deficiency is a widespread health problem particularly in countries where rice is a major constituent of the diet, since grain polishing removes most of the thiamin in the bran. Therefore, it is of major interest to define the pathway of biosynthesis, a virtually unexplored area in plants, which may assist in the overproduction of the vitamin for beneficial purposes. On the other hand, vitamin B6 is renowned as being involved in more functions than any other single nutrient being a cofactor for a diverse array of enzymes ranging from amino acid metabolism to antibiotic biosynthesis. In plants, it is also used in many secondary metabolite pathways e.g. alkaloid biosynthesis. More recently, some novel functions have been revealed for both of these vitamins that go beyond their role as cofactors. Vitamin B6 has been shown to be an antioxidant with potency equivalent to those of vitamins C and E, and has been implicated in alleviating oxidative, UV and salt stress in plants, while vitamin B1 has been linked to systemic acquired resistance in plants, in addition to DNA damage tolerance. The involvement of vitamins B1 and B6 in stress responses was completely unprecedented and may be of economical importance in the development of stress-tolerant crops. Furthermore, as the biosynthesis pathways exist in only bacteria, fungi and plants i.e. being absent from humans, they may provide novel drug targets. Therefore, the aims of this research are to establish the pathways of biosynthesis, decipher how their production is regulated, dissect modes of transport, assess effects of over- or under- accumulation and unravel novel roles of vitamins B1 and B6 and their mechanisms. An interdisciplinary approach will be taken combining molecular cellular biology, biochemical, biophysical, and physiological methods. The studies will predominantly be carried out in the plant model, Arabidopsis thaliana, but bacterial models will be utilized to decipher data rapidly. While these issues are of fundamental importance and are of broad interest to the scientific community, the answers to these questions may permit either the production of these compounds for beneficial effects or their depletion in the context of herbicide or antibiotic development.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
The last piece in the vitamin B1 biosynthesis puzzle: Structural and functional insight into yeast HMP-P synthase.
Coquille Sandrine, Roux Celine, Fitzpatrick Teresa B, Thore Stephane (2012), The last piece in the vitamin B1 biosynthesis puzzle: Structural and functional insight into yeast HMP-P synthase., in The Journal of biological chemistry, 287(50), 42333-42343.
Vitamin deficiencies in humans: can plant science help?
Fitzpatrick Teresa B, Basset Gilles J C, Borel Patrick, Carrari Fernando, DellaPenna Dean, Fraser Paul D, Hellmann Hanjo, Osorio Sonia, Rothan Christophe, Valpuesta Victoriano, Caris-Veyrat Catherine, Fernie Alisdair R (2012), Vitamin deficiencies in humans: can plant science help?, in The Plant Cell, 24(2), 395-414.
Vitamin B6 in plants: More than meets the eye.
Fitzpatrick Teresa B (2011), Vitamin B6 in plants: More than meets the eye., in Fabrice Rébeillé and Roland Douce (ed.), Elsevier Limited, Ireland, 1-38.
Enhanced levels of vitamin B-6 increase aerial organ size and positively affect stress tolerance in Arabidopsis
Raschke M, Boycheva S, Crevecoeur M, Nunes-Nesi A, Witt S, Fernie AR, Amrhein N, Fitzpatrick TB (2011), Enhanced levels of vitamin B-6 increase aerial organ size and positively affect stress tolerance in Arabidopsis, in The Plant Journal, 66(3), 414-432.
It takes two to tango: defining an essential second active site in pyridoxal 5'-phosphate synthase.
Moccand Cyril, Kaufmann Markus, Fitzpatrick Teresa B (2011), It takes two to tango: defining an essential second active site in pyridoxal 5'-phosphate synthase., in PloS one, 6(1), 16042-16042.
Vitamin B6 biosynthesis: charting the mechanistic landscape.
Fitzpatrick Teresa B, Moccand Cyril, Roux Céline (2010), Vitamin B6 biosynthesis: charting the mechanistic landscape., in Chembiochem : a European journal of chemical biology, 11(9), 1185-93.
GintPDX1 encodes a protein involved in vitamin B6 biosynthesis that is up-regulated by oxidative stress in the arbuscular mycorrhizal fungus Glomus intraradices
Benabdellah K, Azcon-Aguilar C, Valderas A, Speziga D, Fitzpatrick Teresa B, Ferrol N (2009), GintPDX1 encodes a protein involved in vitamin B6 biosynthesis that is up-regulated by oxidative stress in the arbuscular mycorrhizal fungus Glomus intraradices, in New Phytologist, 184(3), 682-693.
Intersubunit cross-talk in pyridoxal 5'-phosphate synthase, coordinated by the C terminus of the synthase subunit.
Raschle Thomas, Speziga David, Kress Wolfgang, Moccand Cyril, Gehrig Peter, Amrhein Nicolas, Weber-Ban Elika, Fitzpatrick Teresa B. (2009), Intersubunit cross-talk in pyridoxal 5'-phosphate synthase, coordinated by the C terminus of the synthase subunit., in Journal of Biological Chemistry, 284, 7706-7718.

Collaboration

Group / person Country
Types of collaboration
Elika Weber-Ban (ETH Zurich) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Stéphane Thore (University of Geneva) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Tadhg Begley (Texas A&M) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Alisdair Fernie (MPI Golm) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Hanjo Hellmann (Washington State University) United States of America (North America)
- Publication
Jürgen Stolz (Technical University Munich) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Ivo Tews, Barbara Kappes (University of Heidelberg) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Klaus Apel (Cornell University) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Duilio Arigoni (ETH Zürich) Switzerland (Europe)
- Research Infrastructure
Prof. Jean-luc Wolfender, University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Nuria Ferrol (CSIC) Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Gordon Research conference: Membrane Transport proteins 01.07.2012 Les Diablerets, Switzerland
Swissplant'12 18.01.2012 Meiringen, Switzerland.
Enzymes, coenzymes and metabolic pathways 17.11.2011 Xcaret, Mexico
SEB Plant Transport Group meeting 2011 14.09.2011 Lancaster, U.K.
Swissplant '11 09.02.2011 Meiringen, Switzerland.
Arc Lémanique Plant Science meeting 08.10.2010 Pully, Switzerland.
Switzerland-Japan workshop on photosynthetic adaptation and chloroplast dynamics 14.01.2010 Villars, Switzerland.
Max Planck Institute for Plant Physiology 09.12.2009 Golm, Germany.
Geneva Biology Club 04.11.2009 Geneva, Switzerland.
Plant ROS meeting 08.07.2009 Helsinki, Finland
VIII European Symposium of The Protein Society 14.06.2009 Zurich, Switzerland.
European Symposium on Bio-organic chemistry 24.04.2009 Gregynog, Wales.
Invited lecture, Universita' degli Studi di Milano 20.03.2009 Milan, Italy
Invited lecture, University of Lausanne 11.03.2009 Lausanne, Switzerland
USGEB 29.01.2009 Interlaken, Switzerland.
Switzerland-Japan workshop on photosynthetic adaptation and chloroplast dynamics. 01.10.2008 Nara, Japan.
Trinational Arabidopsis meeting 10.09.2008 Zurich, Switzerland
Trends in Enzymology 02.07.2008 St. Malo, France


Self-organised

Title Date Place

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions International Fascination of Plants day Rhaeto-Romanic Switzerland 17.05.2012
Other activities European Plant Science Organisation Western Switzerland Rhaeto-Romanic Switzerland
Talks/events/exhibitions Swiss Plant Science Web Rhaeto-Romanic Switzerland German-speaking Switzerland Italian-speaking Switzerland Western Switzerland

Awards

Title Year
Travel grant 2011
Best contribution 2010
Best Poster 2010
Friedrich Miescher Prize 2009
ETH Latsis prize 2008

Associated projects

Number Title Start Funding scheme
141117 Unraveling the molecular mechanisms and regulatory networks controlling responses to thiamin (vitamin B1) or pyridoxine (vitamin B6) in Arabidopsis. 01.11.2012 Project funding (Div. I-III)
145001 Achat d'un appareil Seahorse X-24 pour l'analyse de la fonction respiratoire mitochondriale et d'un instrument de thermophorèse pour l'analyse d'intéractions biomoléculaires 01.01.2013 R'EQUIP
140911 VITRICA: Vitamin B1 & B6 in rice and cassava for enhanced nutritional value and plant stress resistance 01.05.2012 Project funding (Div. I-III)

Abstract

Vitamins are defined as organic micronutrients that must be obtained in the human diet and are essential compounds for the survival of all organisms. Plants are critical sources of these compounds. However, despite this recognition, the importance of these compounds to plants themselves has been somewhat overlooked. Thus, in most cases the physiological, biochemical and molecular mechanisms that contribute to their synthesis, transport and accumulation in plants are not known. This is especially the case for the water-soluble B vitamins. The main focus of the proposed research will be on vitamin B1 (thiamin) and vitamin B6 (pyridoxine). The essentiality of these compounds to all organisms is recognized by their well-established function as coenzymes for numerous metabolic enzymes. Vitamin B1 is necessary for the catalytic activity of enzymes of the citric acid cycle, glycolysis and the pentose phosphate pathway, in addition to amino acid and isoprenoid biosynthesis. Deficiency is a widespread health problem particularly in countries where rice is a major constituent of the diet, since grain polishing removes most of the thiamin in the bran. Therefore, it is of major interest to define the pathway of biosynthesis, a virtually unexplored area in plants, which may assist in the overproduction of the vitamin for beneficial purposes. On the other hand, vitamin B6 is renowned as being involved in more functions than any other single nutrient being a cofactor for a diverse array of enzymes ranging from amino acid metabolism to antibiotic biosynthesis. In plants, it is also used in many secondary metabolite pathways e.g. alkaloid biosynthesis. More recently, some novel functions have been revealed for both of these vitamins that go beyond their role as cofactors. Vitamin B6 has been shown to be an antioxidant with potency equivalent to those of vitamins C and E, and has been implicated in alleviating oxidative, UV and salt stress in plants, while vitamin B1 has been linked to systemic acquired resistance in plants, in addition to DNA damage tolerance. The involvement of vitamins B1 and B6 in stress responses was completely unprecedented and may be of economical importance in the development of stress-tolerant crops. Furthermore, as the biosynthesis pathways exist in only bacteria, fungi and plants i.e. being absent from humans, they may provide novel drug targets. Therefore, the aims of this research are to establish the pathways of biosynthesis, decipher how their production is regulated, dissect modes of transport, assess effects of over- or under- accumulation and unravel novel roles of vitamins B1 and B6 and their mechanisms. An interdisciplinary approach will be taken combining molecular cellular biology, biochemical, biophysical, and physiological methods. The studies will predominantly be carried out in the plant model, Arabidopsis thaliana, but bacterial models will be utilized to decipher data rapidly. While these issues are of fundamental importance and are of broad interest to the scientific community, the answers to these questions may permit either the production of these compounds for beneficial effects or their depletion in the context of herbicide or antibiotic development.
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