Biotin is a water-soluble vitamin required by all organisms, but only synthesized by plants and some bacterial and fungal species. As a cofactor, biotin is responsible for carbon dioxide transfer in all biotin-dependent carboxylases, including acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and pyruvate carboxylase. Adding biotin to carboxylases is catalyzed by the enzyme holocarboxylase synthetase (HCS). Biotin is also involved in gene regulation, and there is some indication that histones can be biotinylated in humans. Histone proteins and most histone modifications are highly conserved among eukaryotes. HCS1 is the only functional biotin ligase in Arabidopsis and has a high homology with human HCS. Therefore, we hypothesized that HCS1 also biotinylates histone proteins in Arabidopsis. A comparison of the catalytic domain of HCS proteins was performed among eukaryotes, prokaryotes, and archaea, and this domain is highly conserved across the selected organisms. Biotinylated histones could not be identified in vivo by using avidin precipitation or two-dimensional gel analysis. However, HCS1 physically interacts with Arabidopsis histone H3 in vitro, indicating the possibility of the role of this enzyme in the regulation of gene expression. 1. Introduction Biotin is a water-soluble, B-complex vitamin that is required by all organisms [1]. The main role of biotin is to serve as a cofactor for carboxylases [2, 3]. Addition of biotin to carboxylases is catalyzed by holocarboxylase synthetase (HCS) in a two-step ATP-dependent reaction [4]. Based on the crystal structure of BirA, the E. coli HCS [3], the first step produces an intermediate biotinyl-5′-AMP (B-AMP). B-AMP is then transferred to a specific lysine residue of the carboxylase with the release of AMP [5]. Five biotin-dependent proteins have been characterized in plants [3]. One of them is a seed-specific protein SBP65 for biotin storage [6, 7]. The other four are all carboxylases: homomeric acetyl-CoA carboxylase, heteromeric acetyl-CoA carboxylase, geranoyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase [8–11]. These enzymes are involved in many important metabolic pathways, such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism [3] (Figure 1). Figure 1: Biotin network in plants. Schematic map of the metabolism associated with biotin. Metabolites’ names are in black text. Red arrows represent the biotinylating actions of HCS on biotin-dependent proteins. Black arrows represent other metabolic reactions characterized in plants. Enzymes identified by direct biochemical
References
[1]
D. A. Bender, Nutrition and Biochemistry of the Vitamins, Academic Press, New York, NY, USA, 1992.
[2]
J. R. Knowles, “The mechanism of biotin-dependent enzymes,” Annual Review of Biochemistry, vol. 58, pp. 195–221, 1989.
[3]
B. J. Nikolau, J. B. Ohlrogge, and E. S. Wurtele, “Plant biotin-containing carboxylases,” Archives of Biochemistry and Biophysics, vol. 414, no. 2, pp. 211–222, 2003.
[4]
A. Chapman-Smith and J. E. Cronan, “The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity,” Trends in Biochemical Sciences, vol. 24, no. 9, pp. 359–363, 1999.
[5]
J. Zempleni and T. Kuroishi, “Biotin,” Advances in Nutrition, vol. 3, no. 2, pp. 213–214, 2012.
[6]
M. Duval, C. Job, C. Alban, R. Douce, and D. Job, “Developmental patterns of free and protein-bound biotin during maturation and germination of seeds of Pisum sativum: characterization of a novel seed-specific biotinylated protein,” The Biochemical Journal, vol. 299, no. 1, pp. 141–150, 1994.
[7]
L. Dehaye, M. Duval, D. Viguier, J. Yaxley, and D. Job, “Cloning and expression of the pea gene encoding SBP65, a seed-specific biotinylated protein,” Plant Molecular Biology, vol. 35, no. 5, pp. 605–621, 1997.
[8]
T. Konishi and Y. Sasaki, “Compartmentalization of two forms of acetyl-CoA carboxylase in plants and the origin of their tolerance toward herbicides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 3598–3601, 1994.
[9]
C. Alban, P. Baldet, and R. Douce, “Localization and characterization of two structurally different forms of acetyl-CoA carboxylase in young pea leaves, of which one is sensitive to aryloxyphenoxypropionate herbicides,” The Biochemical Journal, vol. 300, no. 2, pp. 557–565, 1994.
[10]
M. D. Anderson, P. Che, J. Song, B. J. Nikolau, and E. S. Wurtele, “3-Methylcrotonyl-coenzyme A carboxylase is a component of the mitochondrial leucine catabolic pathway in plants,” Plant Physiology, vol. 118, no. 4, pp. 1127–1138, 1998.
[11]
X. Guan, T. Diez, T. K. Prasad, B. J. Nikolau, and E. S. Wurtele, “Geranoyl-CoA carboxylase: a novel biotin-containing enzyme in plants,” Archives of Biochemistry and Biophysics, vol. 362, no. 1, pp. 12–21, 1999.
[12]
H. Daniel and J. Zempleni, Molecular Nutrition, CABI Publishing, Oxfordshire, UK, 2003.
[13]
R. Rodríguez-Meléndez and J. Zempleni, “Regulation of gene expression by biotin,” The The Journal of Nutritional Biochemistry, vol. 14, no. 12, pp. 680–690, 2003.
[14]
R. S. Solórzano-Vargas, D. Pacheco-Alvarez, and A. León-Del-Río, “Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 8, pp. 5325–5330, 2002.
[15]
P. Che, L. M. Weaver, E. Syrkin Wurtele, and B. J. Nikolau, “The role of biotin in regulating 3-methylcrotonyl-coenzyme a carboxylase expression in Arabidopsis,” Plant Physiology, vol. 131, no. 3, pp. 1479–1486, 2003.
[16]
J. Steven Stanley, J. B. Griffin, and J. Zempleni, “Biotinylation of histones in human cells: effects of cell proliferation,” European Journal of Biochemistry, vol. 268, no. 20, pp. 5424–5429, 2001.
[17]
M. A. Narang, R. Dumas, L. M. Ayer, and R. A. Gravel, “Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase,” Human Molecular Genetics, vol. 13, no. 1, pp. 15–23, 2004.
[18]
N. Kothapalli, G. Sarath, and J. Zempleni, “Biotinylation of K12 in histone H4 decreases in response to DNA double-strand breaks in human JAr choriocarcinoma cells,” Journal of Nutrition, vol. 135, no. 10, pp. 2337–2342, 2005.
[19]
L. Rios-Avila, V. Pestinger, and J. Zempleni, “K16-biotinylated histone H4 is overrepresented in repeat regions and participates in the repression of transcriptionally competent genes in human Jurka,” The Journal of Nutritional Biochemistry, vol. 23, no. 12, pp. 1559–1564, 2012.
[20]
J. Fuchs, D. Demidov, A. Houben, and I. Schubert, “Chromosomal histone modification patterns—from conservation to diversity,” Trends in Plant Science, vol. 11, no. 4, pp. 199–208, 2006.
[21]
J. Puyaubert, L. Denis, and C. Alban, “Dual targeting of Arabidopsis holocarboxylase synthetase1: a small upstream open reading frame regulates translation initiation and protein targeting,” Plant Physiology, vol. 146, no. 2, pp. 478–491, 2008.
[22]
K. P. Wilson, L. M. Shewchuk, R. G. Brennan, A. J. Otsuka, and B. W. Matthews, “Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 19, pp. 9257–9261, 1992.
[23]
E. Campeau and R. A. Gravel, “Expression in Escherichia coli of N- and C-terminally deleted human holocarboxylase synthetase. Influence of the N-terminus on biotinylation and identification of a minimum functional protein,” Journal of Biological Chemistry, vol. 276, no. 15, pp. 12310–12316, 2001.
[24]
A. Chapman-Smith, T. D. Mulhern, F. Whelan, J. E. Cronan, and J. C. Wallace, “The C-terminal domain of biotin protein ligase from E. coli is required for catalytic activity,” Protein Science, vol. 10, no. 12, pp. 2608–2617, 2001.
[25]
J. L. K. Van Hove, S. Josefsberg, C. Freehauf et al., “Management of a patient with holocarboxylase synthetase deficiency,” Molecular Genetics and Metabolism, vol. 95, no. 4, pp. 201–205, 2008.
[26]
X. Chen, The analysis of HCS1 in arabidopsis [Ph.D. thesis], Iowa State University, 2011.
[27]
M. A. Larkin, G. Blackshields, N. P. Brown et al., “Clustal W and Clustal X version 2.0,” Bioinformatics, vol. 23, no. 21, pp. 2947–2948, 2007.
[28]
G. Camporeale, E. E. Shubert, G. Sarath, R. Cerny, and J. Zempleni, “K8 and K12 are biotinylated in human histone H4,” European Journal of Biochemistry, vol. 271, no. 11, pp. 2257–2263, 2004.
[29]
K. Kobza, G. Camporeale, B. Rueckert et al., “K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase,” The FEBS Journal, vol. 272, no. 16, pp. 4249–4259, 2005.
[30]
Y. C. Chew, G. Camporeale, N. Kothapalli, G. Sarath, and J. Zempleni, “Lysine residues in N-terminal and C-terminal regions of human histone H2A are targets for biotinylation by biotinidase,” The Journal of Nutritional Biochemistry, vol. 17, no. 4, pp. 225–233, 2006.
[31]
G. Camporeale, C. C. Yap, A. Kueh, G. Sarath, and J. Zempleni, “Use of synthetic peptides for identifying biotinylation sites in human histones,” Methods in Molecular Biology, vol. 418, pp. 139–148, 2008.
[32]
K. Kobza, G. Sarath, and J. Zempleni, “Prokaryotic BirA ligase biotinylates K4, K9, K18 and K23 in histone H3,” Biochemistry and Molecular Biology Reports, vol. 41, no. 4, pp. 310–315, 2008.
[33]
S. Healy, T. D. Heightman, L. Hohmann, D. Schriemer, and R. A. Gravel, “Nonenzymatic biotinylation of histone H2A,” Protein Science, vol. 18, no. 2, pp. 314–328, 2009.
[34]
C. Alban, D. Job, and R. Douce, “Biotin metabolism in plants,” Annual Review of Plant Physiology and Plant Molecular Biology, vol. 51, pp. 17–47, 2000.
[35]
S. Healy, B. Perez-Cadahia, D. Jia, M. K. McDonald, J. R. Davie, and R. A. Gravel, “Biotin is not a natural histone modification,” Biochimica et Biophysica Acta, vol. 1789, no. 11-12, pp. 719–733, 2009.
[36]
L. M. Bailey, R. A. Ivanov, J. C. Wallace, and S. W. Polyak, “Artifactual detection of biotin on histones by streptavidin,” Analytical Biochemistry, vol. 373, no. 1, pp. 71–77, 2008.
[37]
L. Li, C. M. Foster, Q. Gan et al., “Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves,” Plant Journal, vol. 58, no. 3, pp. 485–498, 2009.
[38]
M. Karimi, D. Inzé, and A. Depicker, “GATEWAY vectors for Agrobacterium-mediated plant transformation,” Trends in Plant Science, vol. 7, no. 5, pp. 193–195, 2002.
[39]
U. K. Laemmli, “Cleavage of structural proteins during the assembly of the head of bacteriophage T4,” Nature, vol. 227, no. 5259, pp. 680–685, 1970.
[40]
J. Ke, J. K. Choi, M. Smith, H. T. Horner, B. J. Nikolau, and E. S. Wurtele, “Structure of the CAC1 gene and in situ characterization of its expression: the Arabidopsis thaliana gene coding for the biotin-containing subunit of the plastidic acetyl-coenzyme a carboxylase,” Plant Physiology, vol. 113, no. 2, pp. 357–365, 1997.
[41]
B. L. Fatland, B. J. Nikolau, and E. S. Wurtele, “Reverse genetic characterization of cytosolic acetyl-CoA generation by ATP-citrate lyase in Arabidopsis,” The Plant Cell, vol. 17, no. 1, pp. 182–203, 2005.
[42]
J. N. Rybak, S. B. Scheurer, D. Neri, and G. Elia, “Purification of biotinylated proteins on streptavidin resin: a protocol for quantitative elution,” Proteomics, vol. 4, no. 8, pp. 2296–2299, 2004.
[43]
C. R. Xu, C. Liu, Y. L. Wang et al., “Histone acetylation affects expression of cellular patterning genes in the Arabidopsis root epidermis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 40, pp. 14469–14474, 2005.
