A kinetic framework for modeling oleochemical biosynthesis in Escherichia coli
Abstract
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 Escherichia 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 (FAEEs), for example, suggests that reductions in titer caused by enzyme overexpression—an experimentally consistent phenomenon—can result from shifts in metabolite pools that are incompatible with the substrate specificities of downstream enzymes, and a focused examination of multiple alcohol pathways indicates that coordinated shifts in enzyme concentrations provide a general means of tuning 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 24, 2022
- Source ID
- 10.1002/bit.28209
Entities
People
- Elia C. Cipriano
- Jackson Peoples
- Jerome M Fox
- Kathryn Mains
- Sophia Ruppe
Organizations
- Army Research Office
- National Institutes of Health
- University of Colorado