Thermodynamic analysis of biodegradation pathways

Abstract

Microorganisms provide a wealth of biodegradative potential in the reduction and elimination of xenobiotic compounds in the environment. One useful metric to evaluate potential biodegradation pathways is thermodynamic feasibility. However, experimental data for the thermodynamic properties of xenobiotics is scarce. The present work uses a group contribution method to study the thermodynamic properties of the University of Minnesota Biocatalysis/Biodegradation Database. The Gibbs free energies of formation and reaction are estimated for 914 compounds (81%) and 902 reactions (75%), respectively, in the database. The reactions are classified based on the minimum and maximum Gibbs free energy values, which accounts for uncertainty in the free energy estimates and a feasible concentration range relevant to biodegradation. Using the free energy estimates, the cumulative free energy change of 89 biodegradation pathways (51%) in the database could be estimated. A comparison of the likelihood of the biotransformation rules in the Pathway Prediction System and their thermodynamic feasibility was then carried out. This analysis revealed that when evaluating the feasibility of biodegradation pathways, it is important to consider the thermodynamic topology of the reactions in the context of the complete pathway. Group contribution is shown to be a viable tool for estimating, a priori, the thermodynamic feasibility and the relative likelihood of alternative biodegradation reactions. This work offers a useful tool to a broad range of researchers interested in estimating the feasibility of the reactions in existing or novel biodegradation pathways.

Computational framework for predictive biodegradation

“…We used a group contribution method (Jankowski et al, 2008) to estimate the Gibbs free energy of the individual reactions and calculated the cumulative energy of the pathway. This method provides a means of estimating the thermodynamic properties of biochemical reactions and has been shown to be a viable tool to provide a priori estimates of the thermodynamic feasibility of biodegradation pathways (Finley et al, 2009). We have previously shown how to treat biodegradation reactions involving oxygenase and reductive dechlorination reactions (Finley et al, 2009).…”

“…This method provides a means of estimating the thermodynamic properties of biochemical reactions and has been shown to be a viable tool to provide a priori estimates of the thermodynamic feasibility of biodegradation pathways (Finley et al, 2009). We have previously shown how to treat biodegradation reactions involving oxygenase and reductive dechlorination reactions (Finley et al, 2009). Since much of the free energy released in oxygenase reactions is associated with the reduction of oxygen to water and is not coupled to the generation of electron carriers, we only report the free energy change that is available for cell mass maintenance and growth.…”

Theoretical investigation of the sequential reductive dechlorination pathways of chlorobenzenes and chloroanilines

“…Thus, the difference in dechlorination pathways between experimentally observed and theoretically calculated proves the necessity of a multivariable analysis for field applications. Recently, Finley et al (2009) reported that thermodynamic analysis alone could not predict the biodegradation pathway of xenobiotics. Rather, thermodynamic analysis combined with reaction pathway prediction tools (Ellis et al, 2008) can assist the prediction of degradation pathways of these compounds.…”

Computational screening of novel thiamine-catalyzed decarboxylation reactions of 2-keto acids

“…When applied to a starting substrate and its progeny, all possible enzymatic reactions given these generalized enzyme operators are unfurled, including a large number of novel reactions. For a number of different systems, it has been shown that the computational framework identifies hundreds to thousands of novel biochemical pathways from a starting compound to a target compound [16,20,21]. Various screening methods were applied to cull this large set of novel pathways to a manageable number of attractive candidates, including pathway length, number of novel intermediates, thermodynamic landscape, and pathway flux analysis [22] based on metabolic flux analysis and thermodynamic metabolic flux analysis [15,[23][24][25].…”

“…One approach that has emerged recently utilizes a computational framework based on graph theory that creates complex networks of reactions and compounds based on generalized enzyme reactions [13][14][15][16][17][18][19][20]. Substrates and products of reactions are represented by matrices, and reactions are carried out through addition of reaction operators.…”