A Generalized Computational Framework to Streamline Thermodynamics and Kinetics Analysis of Metabolic Pathways

Wei Xiong, Chao Wu, Huaiguang Jiang, Pin-Ching Maness, Jianping Yu, Isha Kalra, Xin Wang, Melissa Cano

Research output: Contribution to journalArticlepeer-review

24 Scopus Citations


Metabolic engineering is a critical biotechnological approach in addressing global energy and environment challenges. Most engineering efforts, however, consist of laborious and inefficient trial-and-error of target pathways, due in part to the lack of methodologies that can comprehensively assess pathway properties in thermodynamics and kinetics. Metabolic engineering can benefit from computational tools that evaluate feasibility, expense and stability of non-natural metabolic pathways. Such tools can also help us understand natural pathways and their regulation at systems level. Here we introduce a computational toolbox, PathParser, which, for the first time, integrates multiple important functions for pathway analysis including thermodynamics analysis, kinetics-based protein cost optimization and robustness analysis. Specifically, PathParser enables optimization of the driving force of a pathway by minimizing the Gibbs free energy of least thermodynamically favorable reaction. In addition, based on reaction thermodynamics and enzyme kinetics, it can compute the minimal enzyme protein cost that supports metabolic flux, and evaluate pathway stability and flux in response to enzyme concentration perturbations. In a demo analysis of the Calvin–Benson–Bassham cycle and photorespiration pathway in the model cyanobacterium Synechocystis PCC 6803, the computation results are corroborated by experimental proteomics data as well as metabolic engineering outcomes. This toolbox may have broad application in metabolic engineering and systems biology in other microbial systems.

Original languageAmerican English
Pages (from-to)140-150
Number of pages11
JournalMetabolic Engineering
StatePublished - 2020

Bibliographical note

Publisher Copyright:
© 2019 International Metabolic Engineering Society

NREL Publication Number

  • NREL/JA-2700-74433


  • Calvin–Benson–Bassham (CBB) cycle
  • Cyanobacterium
  • Max-min driving force (MDF)
  • Photorespiration
  • Protein cost analysis
  • Robustness analysis


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