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

Synthetic and Systems Biotechnology 2020年第3期5卷 222-229页

作者： Harley Edwards Peng Xu Department of Chemical Biochemical and Environmental EngineeringUniversity of Maryland Baltimore CountyBaltimoreMD21250USA

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 *** fitness and production rates are often complex phenotypes that are governed by highly nonlinear,multivariable functions which are intrinsically linked through carbon *** solution of such dynamic system can be difficult for synthetic biologists to visualize or ***,researchers(Santala et al.,***.,2018)have implemented an arabinose based genetic switch to dynamically partition the central carbon flux between cell growth and product *** autonomous switch allowed dynamic shift from arabinose-associated cell growth to acetate-associated product(wax ester)*** 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 *** 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 with the experimental *** assessing physiologically-accessible parameter space,we observed a wide range of dynamic behavior and examined the different limiting *** solutions for this dynamic system can be viewed simultaneously and resolved in real time via buttons on the graphical user interface(GUI).Metabolic bottlenecks in the system can be accurately predicted by varying the respective rate *** GUI serves as a diagnosis toolkit to troubleshoot genetic circuits design constraints and as an interactive workflow of using this arabinose based genetic switch to dynamically control carbon flux,which may provide a valuable computational toolbox for metabolic engineers and synthetic biologists to simulate and understand complex genetic-metabol

关键词： Metabolic switches Biophysical models Dynamic control Metabolic engineering Central carbon flux intelligent biomanufacturing Green chemistry

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