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A Kinetic Framework for Modeling Oleochemical Biosynthesis in E. coli
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  • Jackson Peoples,
  • Sophia Ruppe,
  • Kathryn Mains,
  • Elia C. Cipriano,
  • Jerome Fox
Jackson Peoples
University of Colorado Boulder

Corresponding Author:[email protected]

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Sophia Ruppe
University of Colorado Boulder
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Kathryn Mains
University of Colorado Boulder
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Elia C. Cipriano
University of Colorado Boulder
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Jerome Fox
University of Colorado Boulder
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Microorganisms build fatty acids with biocatalytic assembly lines, or fatty acid synthases (FASs), that can be repurposed to produce a broad set of fuels and chemicals. Despite their versatility, the product profiles of FAS-based pathways are challenging to adjust without experimental iteration, and off-target products are common. This study uses a detailed kinetic model of the E. coli FAS as a foundation to model nine oleochemical pathways. These models provide good fits to experimental data and help explain unexpected results from in vivo studies. An analysis of pathways for alkanes and fatty acid ethyl esters, for example, suggests that reductions in titer caused by enzyme overexpression can result from shifts in pools of metabolic intermediates that are incompatible with the substrate specificities of downstream enzymes. In general, different engineering objectives (i.e., production, unsaturated fraction, and average chain length) show experimentally consistent sensitivities to pathway enzymes, and model-based compositional analyses indicate simple shifts in enzyme concentrations can alter the product profiles of pathways with promiscuous components. The study concludes by integrating all models into a graphical user interface. The models supplied by this work provide a versatile kinetic framework for studying oleochemical pathways in different biochemical contexts.
03 Jun 2022Submitted to Biotechnology and Bioengineering
03 Jun 2022Submission Checks Completed
03 Jun 2022Assigned to Editor
12 Jun 2022Reviewer(s) Assigned
24 Jul 2022Review(s) Completed, Editorial Evaluation Pending
24 Jul 2022Editorial Decision: Revise Minor
02 Aug 20221st Revision Received
02 Aug 2022Submission Checks Completed
02 Aug 2022Assigned to Editor
07 Aug 2022Review(s) Completed, Editorial Evaluation Pending
07 Aug 2022Editorial Decision: Accept
12 Aug 2022Published in Biotechnology and Bioengineering. 10.1002/bit.28209