Encoding microbial metabolic logic: predicting biodegradation

Abstract

Prediction of microbial metabolism is important for annotating genome sequences and for understanding the fate of chemicals in the environment. A metabolic pathway prediction system (PPS) has been developed that is freely available on the world wide web (http://umbbd.ahc.umn.edu/predict/), recognizes the organic functional groups found in a compound, and predicts transformations based on metabolic rules. These rules are designed largely by examining reactions catalogued in the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) and are generalized based on metabolic logic. The predictive accuracy of the PPS was tested: (1) using a 113-member set of compounds found in the database, (2) against a set of compounds whose metabolism was predicted by human experts, and (3) for consistency with experimental microbial growth studies. First, the system correctly predicted known metabolism for 111 of the 113 compounds containing C and H, O, N, S, P and/or halides that initiate existing pathways in the database, and also correctly predicted 410 of the 569 known pathway branches for these compounds. Second, computer predictions were compared to predictions by human experts for biodegradation of six compounds whose metabolism was not described in the literature. Third, the system predicted reactions liberating ammonia from three organonitrogen compounds, consistent with laboratory experiments showing that each compound served as the sole nitrogen source supporting microbial growth. The rule-based nature of the PPS makes it transparent, expandable, and adaptable.

Metabolism of the Antituberculosis Drug Ethionamide

“…The appearance of new data about the type of metabolite formed can be clarified by other research works involving the metabolism of thioamides [47,48]. Thioamide could be metabolized to support bacterial growth but the mechanism of nitrogen release was not established [47].…”

Metabolism of the Antituberculosis Drug Ethionamide

“…The appearance of new data about the type of metabolite formed can be clarified by other research works involving the metabolism of thioamides [47,48]. Thioamide could be metabolized to support bacterial growth but the mechanism of nitrogen release was not established [47].…”

Metabolic pathway prediction based on inclusive relation between cyclic substructures

“…Some researchers have predicted more than 200,000 metabolites for the plant kingdom and the number of plant species is predicted to be around 400,000 in the world (Hostettmann 2000). Thus, experimental evidence is insufficient for assigning all metabolites to metabolic pathways.There are several approaches for pathway prediction such as fingerprints (Tohsato and Nishimura 2008), reaction rule-base (Langowski and Long 2002;Talafous et al 1994;Ellis et al 2006;Hou et al 2004;Oh et al 2007) and maximum common subgraph search (MCSS) (Kotera et al 2008). The fingerprint-based approach predefines some important molecular fragments and determines which fragments are included in each metabolite as bit-strings consisting of 0's and 1's.…”

“…There are several approaches for pathway prediction such as fingerprints (Tohsato and Nishimura 2008), reaction rule-base (Langowski and Long 2002;Talafous et al 1994;Ellis et al 2006;Hou et al 2004;Oh et al 2007) and maximum common subgraph search (MCSS) (Kotera et al 2008). The fingerprint-based approach predefines some important molecular fragments and determines which fragments are included in each metabolite as bit-strings consisting of 0's and 1's.…”