Monitoring of nutrient limitation in growing E. coli: A mathematical model of a ppGpp-based biosensor

Pokhilko, A. (2017) Monitoring of nutrient limitation in growing E. coli: A mathematical model of a ppGpp-based biosensor. BMC Systems Biology, 11, 106. (doi: 10.1186/s12918-017-0490-5) (PMID:29157236) (PMCID:PMC5697348)

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Abstract

Background: E. coli can be used as bacterial cell factories for production of biofuels and other useful compounds. The efficient production of the desired products requires careful monitoring of growth conditions and the optimization of metabolic fluxes. To avoid nutrient depletion and maximize product yields we suggest using a natural mechanism for sensing nutrient limitation, related to biosynthesis of an intracellular messenger - guanosine tetraphosphate (ppGpp). Results: We propose a design for a biosensor, which monitors changes in the intracellular concentration of ppGpp by coupling it to a fluorescent output. We used mathematical modelling to analyse the intracellular dynamics of ppGpp, its fluorescent reporter, and cell growth in normal and fatty acid-producing E. coli lines. The model integrates existing mechanisms of ppGpp regulation and predicts the biosensor response to changes in nutrient state. In particular, the model predicts that excessive stimulation of fatty acid production depletes fatty acid intermediates, downregulates growth and increases the levels of ppGpp-related fluorescence. Conclusions: Our analysis demonstrates that the ppGpp sensor can be used for early detection of nutrient limitation during cell growth and for testing productivity of engineered lines.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pokhilko, Dr Alexandra
Authors: Pokhilko, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:BMC Systems Biology
Publisher:BioMed Central
ISSN:1752-0509
ISSN (Online):1752-0509
Copyright Holders:Copyright © 2017 The Author
First Published:First published in BMC Systems Biology 11: 106
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
589142A platform for rapid and precise DNA module rearrangements in Synthetic BiologyWilliam StarkBiotechnology and Biological Sciences Research Council (BBSRC)BB/K003356/1RI MOLECULAR CELL & SYSTEMS BIOLOGY