Discovery of Key Molecular Pathways of C1 Metabolism and Formaldehyde Detoxification in Maize through a Systematic Bioinformatics Literature Review
Author(s)
P. Deonikar1,
S. Kothandaram1,
M. Mohan1,
Cori Kollin2,
Phoebe Konecky2,
Rachael Olovyanniko2,
Zachary Zamore2,
Brian Carey2,
V. A. S. Ayyadurai1*
Affiliation(s)
1 International Center for Integrative Systems, Cambridge, MA, USA. 2 Livingston High School, Livingston, NJ, USA.
1 International Center for Integrative Systems, Cambridge, MA, USA. 2 Livingston High School, Livingston, NJ, USA.
ABSTRACT
Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question; 2) literature collection based on a parallel search strategy; 3) relevant study selection based on search refinement; 4) molecular pathway identification; and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis; b) the methylation cycle; and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.
Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question; 2) literature collection based on a parallel search strategy; 3) relevant study selection based on search refinement; 4) molecular pathway identification; and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis; b) the methylation cycle; and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.
KEYWORDS
Systematic Review, Bioinformatics, Molecular Pathway, C1 Metabolism, Formaldehyde, Detoxification, Maize, Methionine Biosynthesis, Methylation Cycle, Folate-Mediated Pathways
Systematic Review, Bioinformatics, Molecular Pathway, C1 Metabolism, Formaldehyde, Detoxification, Maize, Methionine Biosynthesis, Methylation Cycle, Folate-Mediated Pathways
Cite this paper
Deonikar, P. , Kothandaram, S. , Mohan, M. , Kollin, C. , Konecky, P. , Olovyanniko, R. , Zamore, Z. , Carey, B. and Ayyadurai, V. (2015) Discovery of Key Molecular Pathways of C1 Metabolism and Formaldehyde Detoxification in Maize through a Systematic Bioinformatics Literature Review. Agricultural Sciences, 6, 571-585. doi: 10.4236/as.2015.65056.
Deonikar, P. , Kothandaram, S. , Mohan, M. , Kollin, C. , Konecky, P. , Olovyanniko, R. , Zamore, Z. , Carey, B. and Ayyadurai, V. (2015) Discovery of Key Molecular Pathways of C1 Metabolism and Formaldehyde Detoxification in Maize through a Systematic Bioinformatics Literature Review. Agricultural Sciences, 6, 571-585. doi: 10.4236/as.2015.65056.
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http://dx.doi.org/10.1104/pp.016915
[1] Khan, K.S., Kunz, R., Kleijnen, J. and Antes, G. (2003) Five Steps to Conducting a Systematic Review. Journal of the Royal Society of Medicine, 96, 118-121.
http://dx.doi.org/10.1258/jrsm.96.3.118 [2] Ayyadurai, V.A.S. and Dewey, C.F. (2011) CytoSolve: A Methodology for Dynamic Integration of Multiple Molecular Pathway Models. Cellular and Molecular Bioengineering, 4, 28-45.
http://dx.doi.org/10.1007/s12195-010-0143-x [3] Hanson, A.D., Gage, D.A. and Shachar-Hill, Y. (2000) Plant One-Carbon Metabolism and Its Engineering. Trends in Plant Science, 5, 206-213.
http://dx.doi.org/10.1016/S1360-1385(00)01599-5 [4] Hanson, A.D. and Roje, S. (2001) One-Carbon Metabolism in Higher Plants. Annual Review of Plant Physiology and Plant Molecular Biology, 52, 119-137.
http://dx.doi.org/10.1146/annurev.arplant.52.1.119 [5] Ho, M.-W., Saunders, P. and Sirinathsinghji, E. (2013) Science in Society 58 (Institute of Science in Soc). [6] Giese, M., Bauer-Doranth, U., Langebartels, C. and Sandermann, H. (1994) Detoxification of Formaldehyde by the Spider Plant (ChlorophytumcomosumL.) and by Soybean (Glycine max L.) Cell-Suspension Cultures. Plant Physiology, 104, 1301-1309. [7] Xu, Z., Wang, L. and Hou, H. (2011) Formaldehyde Removal by Potted Plant-Soil Systems. Journal of Hazardous Materials, 192, 314-318.
http://dx.doi.org/10.1016/j.jhazmat.2011.05.020 [8] Achkor, H., Díaz, M., Fernández, M.R., Biosca, J.A., Parés, X. and Martínez, M.C. (2003) Enhanced Formaldehyde Detoxification by Overexpression of Glutathione-Dependent Formaldehyde Dehydrogenase from ARABIDOPSIS. Plant Physiology, 132, 2248-2255.
http://dx.doi.org/10.1104/pp.103.022277 [9] Oliver, D.J. (1981) Role of Glycine and Glyoxylate Decarboxylation in Photorespiratory CO2 Release. Plant Physiology, 68, 1031-1034.
http://dx.doi.org/10.1104/pp.68.5.1031 [10] Caperelli, C.A., Benkovic, P.A., Chettur, G. and Benkovicl, S.J. (1980) Purification of a Complex Catalyzing Folate Cofactor Synthesis and Transformylation in de Novo Purine Biosynthesis. Journal of Biological Chemistry, 255, 1885-1890. [11] Sekhon, R.S., Lin, H., Childs, K.L., et al. (2011) Genome-Wide Atlas of Transcription during Maize Development. The Plant Journal, 66, 553-563.
http://dx.doi.org/10.1111/j.1365-313X.2011.04527.x [12] Chen, L., Chan, S.Y. and Cossins, E.A. (1997) Distribution of Folate Derivatives and Enzymes for Synthesis of 10-Formyltetrahydrofolate in Cytosolic and Mitochondrial Fractions of Pea Leaves. Plant Physiology, 115, 299-309. [13] Hanson, A.D. and Gregory, J.F. (2011) Folate Biosynthesis, Turnover, and Transport in Plants. Annual Review of Plant Biology, 62, 105-125.
http://dx.doi.org/10.1146/annurev-arplant-042110-103819 [14] Rébeillé, F., Stephane, R., Jabrin, S., Douce, R., Storozhenko, S. and Van Der Straeten, D. (2006) Folates in Plants?: Biosynthesis, Distribution, and Enhancement. Physiologia Plantarum, 126, 330-342.
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