Historic Microbe Sequenced in BER Microbial Genome Program

The Science

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.

The Impact

The Clostridia are a diverse group of gram-positive, rod-shaped anaerobes that include several toxin-producing pathogens (notably Clostridium difficile, Clostridium botulinum, Clostridium tetani, and Clostridium perfringens) and a large number of terrestrial species that produce acetone, butanol, ethanol, isopropanol, and organic acids through fermentation of a variety of carbon sources. The complete 3.94 million base pair genome of the historic, chemical solvent-producing microbe, Clostridium acetobutylicum, has been sequenced by Douglas Smith at Genome Therapeutics Corp and annotated by Michael Daly of the Uniformed Services University of the Health Sciences. In 1916, Dr. Chaim Weizmann, working in Britain, discovered that C. acetobutylicum could manufacture acetone (desperately needed during World War 1 for munitions production) and British Prime Minister David Lloyd George’s gratitude to Weizmann figured importantly in the decision of the British government in 1917 to issue the Balfour Declaration supporting a Jewish homeland in Palestine. When the state of Israel was founded in 1948, Weizmann became its first President. C. acetobutylicum, which can make ethanol and butanol as well as acetone, is the 10th complete microbial genome sequenced under BER Microbial Genome Program grants and published. An additional 9 microbial genomes have been completed but not yet published.

BER Program Manager

Ramana Madupu

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]


Supported by grants from the Biological and Environmental Research (BER) Program.


Nölling, J., G. Breton, M. V. Omelchenko, K. S. Makarova, Q. Zeng, R. Gibson, H. M. Lee, J. Dubois, D. Qiu, J. Hitti, GTC Sequencing Center Production, Finishing, and Bioinformatics Teams, Y. I. Wolf, R. L. Tatusov, F. Sabathe, L. Doucette-Stamm, P. Soucaille, M. J. Daly, G. N. Bennett, E. V. Koonin, and D. R. Smith. “Genome Sequence and Comparative Analysis of the Solvent-Producing Bacterium Clostridium acetobutylicum,” Journal of Bacteriology 183(16), 4823–38. DOI:10.1128/JB.183.16.4823-4838.2001.