System Biology of Clostridium acetobutylicum
- a possible answer to dwindling crude oil reserves
The genus Clostridium are obligately anaerobic, Gram-positive, spore-forming rods. Some species cause devastating diseases. Thus, the European healthcare system is currently under considerable pressure from the relentless rise in C.difficile infection rates, C.perfringens-induced necrotic enteritis has re-emerged as a serious economic issue for the poultry industry following the withdrawal of antibiotic growth promoters, whilst old foes, such as C.botulinum, pose renewed threats in the hands of the bioterrorist. On the other hand, most clostridial species are entirely benign, and their extreme metabolic diversity is being pursued as biocatalysts in the generation of chemicals from renewal biomass. Principle amongst these is C. acetobutylicum, an organism with a longstanding history in the commercial production of solvents.
Despite their importance, our understanding of their biology has lagged behind their aerobic counterparts, Bacillus. With the advent of the genomic era, the situation has changed. Seven genome sequences have been completed. The first was that of C. acetobutylicum, a reflection of its commercial importance and the wealth of available physiological data. Indeed, with the most highly developed set of genetic tools, C. acetobutylicum is considered the “E.coli“ of the clostridial world.
Our overall goal is, therefore, to establish C.acetobutylicum as the paradigm for clostridial systems biology. The focus will be on the key regulatory and metabolic events that occur during the transition between acidogenic, vegetative growth and the onset of solvent production and sporulation. Specific workpackages will seek to identify and quantify the changes taking place, and the regulatory mechanisms involved, to determine the role of cell density (quorum sensing) in the transition, to evaluate the significance of redox state and glycosylation, and to establish how the organisms copes with, and reacts to, stress. The dynamic, quantitative data obtained will be used to mathematically model the various interactions at the cellular level. These aims will be progressed through a combination of disciplines (genetics, transcriptomics, proteomics, metabolomics, biochemistry, chemical engineering and mathematical modelling) deployed by a consortium of eleven European scientists, from three member states (UK, D & NL).
The ability to more effectively predict the behavioural and metabolic response of clostridia will enable the more effective exploitation of C.acetobutylicum in the commercial production of solvents and as an anti-cancer deliver vehicle. It will also lead to a greater understanding of the biology of pathogenic species and, ultimately, to the development of more effective medical countermeasures.
