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

Hdl Handle:
http://hdl.handle.net/10034/617860
Title:
A mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate development
Authors:
Salcedo-Sora, J. Enrique; Mc Auley, Mark T.
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.
Affiliation:
Liverpool Hope University, University of Chester
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
Publication Date:
15-Jan-2016
URI:
http://hdl.handle.net/10034/617860
DOI:
10.1039/C5MB00801H
Additional Links:
http://pubs.rsc.org/is/content/articlelanding/2016/mb/c5mb00801h#!divAbstract
Type:
Article
Language:
en
ISSN:
1742-206X
EISSN:
1742-2051
Appears in Collections:
Chemical Engineering

Full metadata record

DC FieldValue Language
dc.contributor.authorSalcedo-Sora, J. Enriqueen
dc.contributor.authorMc Auley, Mark T.en
dc.date.accessioned2016-08-02T18:29:42Z-
dc.date.available2016-08-02T18:29:42Z-
dc.date.issued2016-01-15-
dc.identifier.citationEnrique 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/C5MB00801Hen
dc.identifier.issn1742-206X-
dc.identifier.doi10.1039/C5MB00801H-
dc.identifier.urihttp://hdl.handle.net/10034/617860-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.publisherRoyal Society of Chemistryen
dc.relation.urlhttp://pubs.rsc.org/is/content/articlelanding/2016/mb/c5mb00801h#!divAbstracten
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectfolate metabolismen
dc.subjectcomputational modellingen
dc.titleA mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate developmenten
dc.typeArticleen
dc.identifier.eissn1742-2051-
dc.contributor.departmentLiverpool Hope University, University of Chesteren
dc.identifier.journalMolecular Biosystemsen
dc.date.accepted16-01-15-
or.grant.openaccessYesen
rioxxterms.funderunfundeden
rioxxterms.identifier.projectunfundeden
rioxxterms.versionSMURen
rioxxterms.licenseref.startdate2017-01-16-
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