Towards a Synthetic Biology of the Stress-Response and the Tolerance Phenotype: Systems Understanding and Engineering of the Clostridium acetobutylicum Stress-Response and Tolerance to Toxic Metabolites

  • Eleftherios T. Papoutsakis
  • Keith V. Alsaker


We discuss experimental and computational systems-biology approaches to support the development of more toxic-metabolite tolerant strains, with emphasis on solventogenic clostridia. We also discuss ideas that have the potential to move the field towards the development of integrated, predictive models of the metabolic and regulatory networks of the stress response to toxic metabolites. Clostridia are Gram+, obligate anaerobic, endospore forming bacteria of major importance to fermentative production of biofuels and chemicals from renewables. We focus on efforts to understand, model and exploit the stress-response of Clostridium acetobutylicum to important toxic metabolites: butanol, butyrate, and acetate. This is a problem of profound and general importance not only in clostridial biotechnologies and systems, but in all microbial systems of interest for bioenergy and chemicals production. Furthermore, the analyses and approaches discussed here are expected to be generalizable and applicable to a much broader set of microorganisms of interest to the production of biofuels and chemicals from renewable sources.


Synthetic biology Stress response Tolerance Engineering Clostridium acetobutylicum Toxic metabolites Systems biology Metabolic model Regulatory model Butanol Butyrate Acetate Bioenergy Chemicals Biofuels Renewable resources Multigenic phenotypes Transcriptional stressome Heat shock proteins Stress regulon Membrane modifications Gene expression Anaerobic Cellulosic material Biorefinery Evolutionary engineering DNA libraries Central metabolism Nitrogen metabolism 



We thank Sergios Nicolaou for discussions, and Dr. Carles Paredes for helpful discussions and assistance with the chi-squared tests. This work was supported in part by Office of Naval Research (USA) Grant N000141010161, by National Science Foundation (USA) grant CBET-1033926, and by Department of Energy (USA) grant DE-SC0007092. K.V.A. was supported in part by an NIH/NIGMS Biotechnology Training Grant (T32-GM08449).


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Eleftherios T. Papoutsakis
    • 1
  • Keith V. Alsaker
    • 2
  1. 1.Molecular Biotechnology Laboratory, Delaware Biotechnology Institute, The Department of Chemical & Biomolecular EngineeringUniversity of DelawareNewarkUSA
  2. 2.Amyris, Inc.EmeryvilleUSA

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