Identification of Growth-Coupled and Kinetically Robust Production in Strain Designs using Genome-Scale Models.

摘要

Conversion of renewable biomass to useful molecules in microbial cell factories can be approached in a rational and systematic manner using constraint-based reconstruction and analysis. Filtering for high confidence in silico designs is critical as in vivo construction and testing is expensive and time consuming. As such, a workflow was devised to analyze the robustness of growth-coupled production against variability in enzyme kinetic parameters through applying a genome-scale model of metabolism and macromolecules expression (ME-model). A collection of 2632 knockout designs in E. coli was evaluated by a workflow that removed 40 redundant knockouts and returned pools of 634 growth-coupled designs and 41 ME-model robust designs. The resulting knockout strategies revealed how enzyme efficiency and pathway tradeoffs can affect growth-coupled production phenotypes.