title: Modelling the role of CtfA/B in reverse shift continuous culture experiments of Clostridium acetobutylicum.
abstract: In continuous phosphate-limited conditions, under pH control from high pH (pH ≳ 5.2) to low pH (pH ≲ 5.2), the metabolism of the Gram-positive bacterium Clostridium acetobutylicum,switches from acid to solvent production. Three main enzymes are responsible for the shift, acetoacetate decarboxylase (Adc), alcohol dehydrogenase (AdhE1/2) and a CoA-transferase (CtfA/B), which are produced in increased quantities during solventogenesis. A two-population model, Millat et al. (2013) and fitted to such 'forward'-shift data, can explain this, as well as observed changes in optical density immediately following the shift: an acidogenic subpopulation is washed out and a solventogenic subpopulation grows in its place, each with distinct physiologies and proteomes. We fit this model to a 'reverse'-shift experiment, where the pH is increased from solventogenic to acidogenic conditions. We find corresponding changes in reaction rates, with AdhE1 and Adc production falling, as in the 'forward' experiments; however, for CtfA/B, the best fit surprisingly arises from the same level of production in both conditions. We propose experiments that would test whether this is a model artefact or accurately reflects cultures shifted in this reverse direction, and, if true, may suggest that over-expressing CtfA/B in both solventogenic and acidogenic conditions could improve the efficiency of fermentation.
authors.affiliation: School of Mathematical Sciences, Mathematical Sciences Building, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: graeme.thorn@nottingham.ac.uk.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Thorn
authors.affiliation: School of Mathematical Sciences, Mathematical Sciences Building, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: john.king@nottingham.ac.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: King
mesh_terms: D000096:Acetone / Q000378:metabolism*; D000440:Butanols / Q000378:metabolism*; D046969:Clostridium acetobutylicum / Q000378:metabolism*; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D005285:Fermentation / Q000502:physiology*; D008954:Models, Biological
chemical_list: D000440:Butanols; D000096:Acetone; D015256:Coenzyme A-Transferases
keywords: AB fermentation; Clostridium acetobutylicum; ODE modelling; Systems biology