Integrated, systems metabolic picture of acetone-butanol-ethanol fermentation by Clostridium acetobutylicum

Chen Liao, Seung Oh Seo, Venhar Celik, Huaiwei Liu, Wentao Kong, Yi Wang, Hans Blaschek, Yong Su Jin, Ting Lu

Research output: Contribution to journalArticlepeer-review

Abstract

Microbial metabolism involves complex, system-level processes implemented via the orchestration of metabolic reactions, gene regulation, and environmental cues. One canonical example of such processes is acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum, during which cells convert carbon sources to organic acids that are later reassimilated to produce solvents as a strategy for cellular survival. The complexity and systems nature of the process have been largely underappreciated, rendering challenges in understanding and optimizing solvent production. Here, we present a system-level computational framework for ABE fermentation that combines metabolic reactions, gene regulation, and environmental cues. We developed the framework by decomposing the entire system into three modules, building each module separately, and then assembling them back into an integrated system. During the model construction, a bottom-up approach was used to link molecular events at the singlecell level into the events at the population level. The integrated model was able to successfully reproduce ABE fermentations of the WT C. acetobutylicum (ATCC 824), as well as its mutants, using data obtained from our own experiments and from literature. Furthermore, the model confers successful predictions of the fermentations with various network perturbations across metabolic, genetic, and environmental aspects. From foundation to applications, the framework advances our understanding of complex clostridial metabolism and physiology and also facilitates the development of systems engineering strategies for the production of advanced biofuels.

Original languageEnglish (US)
Pages (from-to)8505-8510
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number27
DOIs
StatePublished - Jul 7 2015

Keywords

  • ABE fermentation
  • Clostridial physiology
  • Integrated modeling
  • Metabolic engineering
  • Systems biology

ASJC Scopus subject areas

  • General

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