(560a) Novel Reactions To Degrade Xenobiotics

Microorganisms provide a wealth of biodegradative potential in the reduction and elimination of xenobiotic compounds. However, there is a lack of information on the reactions through which biodegradation occurs. In this work, the Biochemical Network Integrated Computational Explorer (BNICE) was applied to predict the biodegradation routes of biphenyl, a substrate used to model the degradation of polychlorinated biphenyls (PCBs). BNICE is a computational framework developed for the generation of all possible reactions and compounds given a set of enzyme reaction rules and starting compounds [1]. BNICE was utilized to generate novel compounds and reactions in two ways: using only the reaction rules involved in the known biodegradation pathway found in the UM-BBD [2], and using the complete set of reaction rules. In this way, we have generated novel biodegradation routes to compounds from the known pathway and have identified additional endpoints with known intermediary metabolism. The number of compounds and reactions generated after each successive application of the reaction rules were monitored. Additionally, a group contribution method for the estimation of thermodynamic properties [3, 4] was used to investigate the thermodynamic feasibility. The cumulative Gibbs free energy of reaction of the known pathway was compared to predicted pathways of the same length.

References

1. Hatzimanikatis, V., et al., Exploring the diversity of complex metabolic networks. Bioinformatics, 2005. 21(8): p. 1603-1609.

2. Ellis, L.B. and L.P. Wackett, The University of Minnesota Biocatalysis/Biodegradation Database: The first decade. Nucleic Acids Research, 2006. 34: p. D517-D521.

3. Jankowski, M.D., et al., Group contribution method for thermodynamic analysis on a genome-scale. 2007. Submitted.

4. Finley, S.D., L.J. Broadbelt, and V. Hatzimanikatis, Thermodynamic analysis of the University of Minnesota Biocatalysis/Biodegradation Database. 2007. Submitted.