Abstract
Folates are key-players in one-carbon metabolism in all organisms. However, only micro-organisms and plants are able to synthesize folates de novo and humans rely entirely on their diet as a sole folate source. As a consequence, folate deficiency is a global problem. Although different strategies are currently implemented to fight folate deficiency, up until now, all of them have their own drawbacks. As an alternative and complementary means to those classical strategies, folate biofortification of rice by metabolic engineering was successfully achieved a couple of years ago. To gain more insight into folate biosynthesis regulation and the effect of folate enhancement on general rice seed metabolism, a transcriptomic study was conducted in developing transgenic rice seeds, overexpressing 2 genes of the folate biosynthetic pathway. Upon folate enhancement, the expression of 235 genes was significantly altered. Here, we show that rice folate biofortification has an important effect on folate dependent, seed developmental and plant stress response/defense processes, but does not affect the expression of the endogenous folate biosynthesis genes.
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Anukul N, Abilgos Ramos R, Mehrshahi P, Castelazo AS, Parker H, Diévart A, Lanau N, Mieulet D, Tucker G, Guiderdoni E, Barrett DA, Bennett MJ (2010) Folate polyglutamylation is required for rice seed development. Rice 3:181–193
Asensi-Fabado MA, Munné-Bosch S (2010) Vitamins in plants: occurrence, biosynthesis and antioxidant function. Trends Plant Sci 10:582–592
Bailey LB (2004) Folate and vitamin B12 recommended intakes and status in the United States. Nutr Rev 62:S14–S20
Basset GJ, Quinlivan EP, Ravanel S, Rébeillé F, Nichols BP, Shinozaki K, Seki M, Adams-Philips LC, Giovannoni JJ, Gregory JF III, Hanson AD (2004a) Folate synthesis in plants: the p-aminobenzoate branch is initiated by a bifunctional PabA-PabB protein that is targeted to plastids. Proc Natl Acad Sci USA 101:1496–1501
Basset GJC, Ravanel S, Quinlivan EP, White R, Giovannoni JJ, Rébeillé F, Nichols BP, Shinozaki K, Seki M, Gregory JF III, Hanson AD (2004b) Folate synthesis in plants: the last step of the p-aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyase. Plant J 40:453–461
Bekaert S, Storozhenko S, Mehrshahi P, Bennett MJ, Lambert W, Gregory JF III, Schubert K, Hugenholtz J, Van Der Straeten D, Hanson AD (2008) Folate biofortification in food plants. Trends Plant Sci 13:28–34
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300
Besson V, Rébeillé F, Neuburger M, Douce R, Cossins EA (1993) Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria. Biochem J 292:425–430
Blancquaert D, Storozhenko S, Loizeau K, De Steur H, De Brouwer V, Viaene J, Ravanel S, Rébeillé F, Lambert W, Van Der Straeten D (2010) Folates and folic acid: from fundamental research toward sustainable health. Crit Rev Plant Sci 29:14–35
Blancquaert D, Navarrete O, Storozhenko S, De Steur H, Van Daele J, Dong W, Lei C, Zhang C, Stove C, Gellynck X, Viaene J, Lambert W, Van Der Straeten D (in press) Biofortified rice to fight folate deficiency. In: Preedy V (ed) Handbook of food fortification and health: from concepts to public health applications. Springer, New York
Canales C, Bhatt AM, Scott R, Dickinson H (2002) EXS, a putative LRR receptor kinase, regulates male germline cell number and tapetal identity and promotes seed development in Arabidopsis. Curr Biol 12:1718–1727
Choi SW, Friso S (2005) Interactions between folate and aging for carcinogenesis. Clin Chem Lab Med 43:1151–1157
Coleman M, Vontas JG, Hemingway J (2002) Molecular characterization of the amplified aldehyde oxidase from insecticide resistant Culex quinquefasciatus. Eur J Biochem 269:768–779
Cook RJ (2001) Disruption of histidine catabolism in NEUT2 mice. Arch Biochem Biophys 392:226–232
Counce PA, Keisling TC, Mitchell AJ (2000) A uniform, objective, and adaptive system for expressing rice development. Crop Sci 40:436–443
De Brouwer V, Storozhenko S, Van De Steene JC, Wille SMR, Stove CP, Van Der Straeten D, Lambert WE (2008) Optimisation and validation of a liquid chromatography–tandem mass spectrometry method for folates in rice. J Chromatogr A 1215:125–132
De Brouwer V, Storozhenko S, Stove CP, Van Daele J, Van Der Straeten D, Lambert WE (2010) Ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for the sensitive determination of folates in rice. J Chromatogr B 878:509–513
Diaz de la Garza RI, Gregory JF III, Hanson AD (2007) Folate biofortification of tomato fruit. Proc Natl Acad Sci USA 104:4218–4222
Endres M, Ahmadi M, Kruman I, Biniszkiewicz D, Meisel A, Gertz K (2005) Folate deficiency increases postischemic brain injury. Stroke 36:321–325
Facella P, Lopez L, Carbone F, Galbraith DW, Guiliano G, Perrota G (2008) Diurnal and circadian rhythms in the tomato transcriptome and their modulation by cryptochrome photoreceptors. PLoS ONE 3:e2798
Garcia D, Saingery V, Chambrier P, Mayer U, Jurgens G, Berger F (2003) Arabidopsis haiku mutants reveal new controls of seed size by endosperm. Plant Physiol 131:1661–1670
Garcia D, Fitz Gerald JN, Berger F (2005) Maternal control of integument cell elongation and zygotic control of endosperm growth are coordinated to determine seed size in Arabidopsis. Plant Cell 17:52–60
Geisel J (2003) Folic acid and neural tube defects in pregnancy—a review. J Perinat Neonatal Nurs 17:268–279
Hanson AD, Roje S (2001) One-carbon metabolism in higher plants. Annu Rev Plant Physiol Plant Mol Biol 52:119–137
Hellemans J, Mortier G, De Paepe A, Speleman F, Vandesompele J (2007) qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8:R19
Hilhorst HWM, Karssen CM (1992) Seed dormancy and germination: the role of abscisic acid and gibberellins and the importance of hormone mutants. Plant Growth Regul 11:225–238
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264
Jiang L, Liu Y, Sun H, Han Y, Li J, Li C, Guo W, Meng H, Li S, Fan Y, Zhang C (2013) The mitochondrial folylpolyglutamate synthetase gene is required for nitrogen utilization during early seedling development in Arabidopsis. Plant Physiol 161:971–989
Johnson JL, Rajagopalan KV (1985) Pterins in other metabolic pathways. In: Blackley RL, Benkovic S (eds) Folates and pterins, vol 2. Wiley, New York, pp 383–399
Johnson DC, Dean DR, Smith AD, Johnson MK (2005) Structure, function, and formation of biological iron–sulfur clusters. Annu Rev Biochem 74:247–281
Kaufman S, Kaufman EE (1985) Tyrosine hydroxylase. In: Blackley RL, Benkovic S (eds) Folates and pterins, vol 2. Wiley, New York, pp 251–352
Krebs HA, Hems R, Tyler B (1976) Regulation of folate and methionine metabolism. Biochem J 158:341–353
Kuhn DM, Lovenberg W (1985) Tryptophan hydroxylase. In: Blackley RL, Benkovic S (eds) Folates and pterins, vol 2. Wiley, New York, pp 115–154
Leydecker MT, Moureaux T, Kraepiel Y, Schnorr K, Caboche M (1995) Molybdenum cofactors mutants, specifically impaired in xanthine dehydrogenase activity and abscisic acid biosynthesis, simultaneously overexpress nitrate reductase. Plant Physiol 107:1427–1431
Li GM, Presnell SR, Gu LY (2003) Folate deficiency, mismatch repair-dependent apoptosis, and human disease. J Nutr Biochem 14:568–575
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25:402–408
Lohse M, Nunes-Nesi A, Krüger P, Nagel A, Hannemann J, Giorgi FM, Childs L, Osorio S, Walther D, Selbig J, Sreenivasulu N, Stitt M, Fernie AR, Usadel B (2010) Robin: an intuitive wizard application for R-based expression microarray quality assessment and analysis. Plant Physiol 153:642–651
Lucock MD, Daskalakis IG, Wild J, Anderson A, Schorah CJ, Lean MEJ, Levene MI (1996) The influence of dietary folate and methionine on the metabolic disposition of endotoxic homocysteine. Biochem Mol Med 59:104–111
Moore JT, Gaylor JL (1969) Isolation and purification of an S-adenosylmethionine: delta 24-sterol methyltransferase from yeast. J Biol Chem 244:6334–6340
Nakase M, Hotta H, Adachi T, Aoki N, Nakamura R, Masumura T, Tanaka K, Matsuda T (1996) Cloning of the rice seed alpha-globulin-encoding gene: sequence similarity of the 5′-flanking region to those of the genes encoding wheat high-molecular-weight glutenin and barley d hordein. Gene 170:223–226
Navarrete O, Van Daele J, Stove C, Lambert W, Van Der Straeten D, Storozhenko S (2012) A folate independent role for cytosolic HPPK/DHPS upon stress in Arabidopsis thaliana. Phytochem 73:23–33
Ori N, Eshed Y, Pinto P, Paran I, Zamir D, Fluhr R (1997) TAO1, a representative of molybdenum cofactor containing hydroxylases from tomato. J Biol Chem 272:1019–1025
Papakostas G, Cassiello CF, Iovieno N (2012) Folates and S-adenosylmethionine for major depressive disorder. Can J Psychiatr 57:406–413
Park E, Rapoport TA (2012) Mechanisms of Sec61/SecY-mediated protein translocation across membranes. Annu Rev Biophys 41:21–40
Sant ME, Lyons SD, Phillips L, Christopherson RI (1991) Antifolates induce inhibition of amido phosphoribosyltransferase in leukemia cells. J Biol Chem 267:11038–11045
Sarafidou T, Kahl C, Martinez-Garay I, Mangelsdorf M, Gesk S, Baker E, Kokkinaki M, Talley P, Maltby EL, French L, Harder L, Hinzmann B, Nobile C, Richkind K, Finnis M, Deloukas P, Sutherland GR, Kutsche K, Moschonas NK, Siebert R, Gecz J (2004) Folate-sensitive fragile site FRA10A is due to an expansion of a CGG repeat in a novel gene, FRA10AC1, encoding a nuclear protein. Genomics 84:69–81
Scott JM, Weir DG (1996) Homocysteine and cardiovascular disease. Q J Med 89:561–563
Scott J, Rébeillé F, Fletcher J (2000) Folic acid and folates: the feasibility for nutritional enhancement in plant foods. J Sci Food Agric 80:795–824
Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PWF, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346:476–483
Smith GK, Mueller WT, Wasserman GF, Taylor WD, Benkovic SJ (1980) Characterization of the enzyme complex involving the folate-requiring enzymes of de novo purine biosynthesis. Biochemistry 19:4313–4321
Sohta Y, Ohta T, Masada M (1997) Purification and some properties of GTP cyclohydrolase I from spinach leafs. Biosci Biotechnol Biochem 61:1081–1085
Stanger O (2004) The potential role of homocysteine in percutaneous coronary interventions (PCI): review of current evidence and plausibility of action. Cell Mol Biol 50:953–988
Storozhenko S, De Brouwer V, Volckaert M, Navarrete O, Blancquaert D, Zhang G-F, Lambert W, Van Der Straeten D (2007) Folate fortification of rice by metabolic engineering. Nat Biotechnol 25:1277–1279
Sutherland GR (2003) Rare fragile sites. Cytogenet Genome Res 100:77–84
Takaiwa F, Oono K, Wing D, Kato A (1991) Sequence of 3 members and expression of a new major subfamily of glutelin genes from rice. Plant Mol Biol 17:875–885
Tanaka T, Antonio BA, Kikuchi S, Matsumoto T, Nagamura Y, Numa H, Sakai H, Wu J, Itoh T, Sasaki T et al (2008) The Rice Annotation Project Database (RAP-DB): 2008 update. Nucleic Acids Res 36:D1028–D1033
Tate PH, Bird AP (1993) Effects of DNA methylation on DNA-binding proteins and gene expression. Curr Opin Genet Dev 3:226–231
The Tomato Genome Consortium (2012) The tomato genome sequence provides insights into fleshy fruit evolution. Nature 485:635–641
Vignols F, Wigger M, Garcia-Garrido JM, Grellet F, Kader J-C, Delseny M (1997) Rice lipid transfer protein (LTP) genes belong to a complex multigene family and are differentially regulated. Gene 195:177–186
Waller JC, Akhtar TA, Lara-Nunez L, Gregory JF III, McQuinn RP, Giovannoni JJ, Hanson AD (2010) Developmental and feedforward control of the expression of folate biosynthesis genes in tomato fruit. Mol Plant 3:66–77
Waller JC, Ellens KW, Alvarez S, Loizeau K, Ravanel S, Hanson AD (2012) Mitochondrial and plastidial COG0354 proteins have folate-dependent functions in iron–sulphur cluster metabolism. J Exp Bot 63:403–411
Yamagata H, Tanaka K, Kasai Z (1982) Evidence for a precursor form of rice glutelin subunits. Agr Biol Chem Tokyo 46:321–322
Yang L, Tada Y, Yamamoto MP, Zhao H, Yoshikawa M, Takaiwa F (2006) A transgenic rice seed accumulation an anti-hypertensive peptide reduces the blood pressure of spontaneously hypertensive rats. FEBS Lett 580:3315–3320
Yoneyama T, Hatakeyama K (1998) Decameric GTP cyclohydrolase I forms complexes with two pentameric GTPCH feedback regulatory proteins in the presence of phenylalanine or of a combination of BH4 and GTP. J Biol Chem 273:20102–20108
Acknowledgments
D.V.D.S. and W.L. gratefully acknowledge financial support from Ghent University (Bijzonder Onderzoeksfonds, BOF2004/GOA/012 and BOF2009/G0A/004), and the Fund for Scientific Research Flanders (FWO, project 3G012609). D.B. was indebted to FWO (Fonds voor Wetenschappelijk Onderzoek—Vlaanderen), for a PhD grant.
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Blancquaert, D., Van Daele, J., Storozhenko, S. et al. Rice folate enhancement through metabolic engineering has an impact on rice seed metabolism, but does not affect the expression of the endogenous folate biosynthesis genes. Plant Mol Biol 83, 329–349 (2013). https://doi.org/10.1007/s11103-013-0091-7
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DOI: https://doi.org/10.1007/s11103-013-0091-7