Unstructured kinetic models to simulate an arabinose switch that decouples cell growth from metabolite production

Synthetic and Systems Biotechnology
Harley Edwards, Peng Xu

Abstract

Modeling synthetic gene circuits to implement dynamic flux balancing is crucial in teaching and exploring metabolic engineering strategies to repartition metabolic precursors and construct efficient microbial cell factories. Microbial fitness and production rates are often complex phenotypes that are governed by highly non-linear, multivariable functions which are intrinsically linked through carbon metabolism. The solution of such dynamic system can be difficult for synthetic biologists to visualize or conceptualize. Recently, researchers (Santala et al., Metab. Eng. Comm., 2018) have implemented an arabinose based genetic switch to dynamically partition the central carbon flux between cell growth and product formation. The autonomous switch allowed dynamic shift from arabinose-associated cell growth to acetate-associated product (wax ester) formation. This system clearly demonstrates the effectiveness of using a genetic switch to decouple cell growth from product formation in a one-pot bioreactor to minimize operational cost. Coupled with Michaelis-Menten kinetics, and Luedeking-Piret equations, we were able to reconstruct and analyze this metabolic switch in silica and achieved graphical solutions that qualitatively match wi...Continue Reading

References

Feb 5, 2000·Nature·M B Elowitz, S Leibler
Feb 5, 2000·Nature·T S GardnerJ J Collins
Apr 23, 2002·Journal of Applied Microbiology·S PapanikolaouI Marc
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nicolas E BuchlerTerence Hwa
Jun 2, 2006·Molecular Systems Biology·Ernesto AndrianantoandroRon Weiss
Feb 16, 2008·FEBS Letters·Rafael Silva-Rocha, Víctor de Lorenzo
May 23, 2009·Nature Reviews. Molecular Cell Biology·Priscilla E M Purnick, Ron Weiss
Oct 27, 2009·Nucleic Acids Research·Ron MiloMichael Springer
Mar 10, 2010·Nature Biotechnology·Jeffrey D OrthBernhard Ø Palsson
Sep 19, 2012·Current Opinion in Biotechnology·Peng XuMattheos A G Koffas
Jul 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Peng XuMattheos Koffas
Nov 27, 2015·Biotechnology for Biofuels·Zhiwei GongZongbao K Zhao
Sep 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Peng XuGregory Stephanopoulos
Mar 16, 2017·Biotechnology and Bioengineering·Peng XuGregory Stephanopoulos
Oct 11, 2017·Metabolic Engineering Communications·Austin D ComerBrian F Pfleger
Nov 18, 2017·Current Opinion in Biotechnology·Peng Xu
Mar 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Stephanie J DoongKristala L J Prather
Sep 28, 2018·Current Opinion in Biotechnology·Tiebin Wang, Mary J Dunlop
Dec 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Christina V Dinh, Kristala L J Prather
Jun 5, 2020·Trends in Biotechnology·Peng XuMattheos Koffas
Jun 22, 2020·Current Opinion in Biotechnology·Monireh MarsafariPeng Xu
Jul 23, 2020·Nature Metabolism·Junyoung O ParkGregory Stephanopoulos

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Citations

Mar 27, 2021·Essays in Biochemistry·Suvi Santala, Ville Santala

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Methods Mentioned

BETA
biosensors

Software Mentioned

ODE23s
Matlab
LaTex
Matlab language package
Windows

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