Coenzyme A-transferase-independent butyrate re-assimilation in Clostridium acetobutylicum - evidence from a mathematical model

Millat, Thomas; Voigt, Christine; Janssen, Holger; Cooksley, Clare M.; Winzer, Klaus; Minton, Nigel P.; Bahl, Hubert; Fischer, Ralf-J�rg; Wolkenhauer, Olaf

Abstract

The hetero-dimeric CoA-transferase CtfA/B is believed to be crucial for the metabolic transition from acidogenesis to solventogenesis in Clostridium acetobutylicum as part of the industrial-relevant acetone-butanol-ethanol (ABE) fermentation. Here, the enzyme is assumed to mediate re-assimilation of acetate and butyrate during a pH-induced metabolic shift and to faciliate the first step of acetone formation from acetoacetyl-CoA. However, recent investigations using phosphate-limited continuous cultures have questioned this common dogma. To address the emerging experimental discrepancies, we investigated the mutant strain Cac-ctfA398s::CT using chemostat cultures. As a consequence of this mutation, the cells are unable to express functional ctfA and are thus lacking CoA-transferase activity. A mathematical model of the pH-induced metabolic shift, which was recently developed for the wild type, is used to analyse the observed behaviour of the mutant strain with a focus on re-assimilation activities for the two produced acids. Our theoretical analysis reveals that the ctfA mutant still re-assimilates butyrate, but not acetate. Based upon this finding, we conclude that C. acetobutylicum possesses a CoA-tranferase-independent butyrate uptake mechanism that is activated by decreasing pH levels. Furthermore, we observe that butanol formation is not inhibited under our experimental conditions, as suggested by previous batch culture experiments. In concordance with recent batch experiments, acetone formation is abolished in chemostat cultures using the ctfa mutant.

Citation

Millat, T., Voigt, C., Janssen, H., Cooksley, C. M., Winzer, K., Minton, N. P., …Wolkenhauer, O. (2014). Coenzyme A-transferase-independent butyrate re-assimilation in Clostridium acetobutylicum - evidence from a mathematical model. Applied Microbiology and Biotechnology, 98(21), https://doi.org/10.1007/s00253-014-5987-x

• Journal Article Type: Article
• Publication Date: Nov 1, 2014
• Deposit Date: Mar 8, 2016
• Publicly Available Date: Mar 8, 2016
• Journal: Applied Microbiology and Biotechnology
• Print ISSN: 0175-7598
• Electronic ISSN: 1432-0614
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 98
• Issue: 21
• DOI: https://doi.org/10.1007/s00253-014-5987-x
• Keywords: Clostridium acetobutylicum; ctfA mutant; Acid re-assimilation; pH-induced metabolic shift; Mathematical modelling
• Public URL: https://nottingham-repository.worktribe.com/output/994004
• Publisher URL: http://link.springer.com/article/10.1007%2Fs00253-014-5987-x
• Additional Information: The final publication is available at Springer via http://dx.doi.org/10.1007/s00253-014-5987-x