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A mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate development

Salcedo-Sora, J. Enrique
; 
Mc Auley, Mark T.
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Affiliation
Liverpool Hope University, University of Chester
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Publication Date
2016-01-15
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Chemical Engineering
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Abstract
The metabolic biochemistry of folate biosynthesis and utilisation has evolved into a complex network of reactions. Although this complexity represents challenges to the field of folate research it has also provided a renewed source for antimetabolite targets. A range of improved folate chemotherapy continues to be developed and applied particularly to cancer and chronic inflammatory diseases. However, new or better antifolates against infectious diseases remain much more elusive. In this paper we describe the assembly of a generic deterministic mathematical model of microbial folate metabolism. Our aim is to explore how a mathematical model could be used to explore the dynamics of this inherently complex set of biochemical reactions. Using the model it was found that: (1) a particular small set of folate intermediates are overrepresented, (2) inhibitory profiles can be quantified by the level of key folate products, (3) using the model to scan for the most effective combinatorial inhibitions of folate enzymes we identified specific targets which could complement current antifolates, and (4) the model substantiates the case for a substrate cycle in the folinic acid biosynthesis reaction. Our model is coded in the systems biology markup language and has been deposited in the BioModels Database (MODEL1511020000), this makes it accessible to the community as a whole.
Citation
Enrique Salcedo-Sora, J., & Mc Auley, M. T. (2016). A mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate development. Molecular BioSystems, 12(3), 923-933. doi: 10.1039/C5MB00801H
Publisher
Royal Society of Chemistry
Journal
Molecular Biosystems
Research Unit
URI
http://hdl.handle.net/10034/617860
DOI
10.1039/C5MB00801H
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PubMed Central ID
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Article
Language
en
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ISSN
1742-206X
EISSN
1742-2051
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http://pubs.rsc.org/is/content/articlelanding/2016/mb/c5mb00801h#!divAbstract