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

Molecular BioSystems
J Enrique Salcedo-Sora, Mark T Mc Auley

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...Continue Reading

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Citations

Nov 3, 2016·The Proceedings of the Nutrition Society·A E MorganM T Mc Auley
Dec 23, 2016·Briefings in Bioinformatics·Mark T Mc AuleyJ Enrique Salcedo-Sora
May 1, 2018·The Proceedings of the Nutrition Society·A E MorganM T Mc Auley
May 23, 2019·Scientific Reports·Aleksandr V ZaitsevFazoil I Ataullakhanov
Nov 18, 2018·Journal of Theoretical Biology·Loukas ZagkosNikos I Kavallaris
Dec 22, 2021·WIREs Mechanisms of Disease·Mark Tomás Mc Auley

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