Introduction to BioTransformation Rule Prioritization

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The basis of the current Pathway Prediction System is a set of metabolic rules. To prioritize metabolic pathways and thus better predict the fate of chemicals in the environment, it is necessary to determine which metabolic rules have precedence over others. This, in turn, depends on what reactions we believe bacteria and fungi will most likely catalyze based on our best present knowledge, a prioritization of reaction likelihood. We ask your help here to do some "homework" to prioritize approximately 50 rules we send you. Please score the rules and return the scored list to us by Monday, May 2, 2005. We will compile these results and this will be one topic of discussion at the workshop. We here define the prioritization process so that all of us will do it the same way.

First, assume that the compound/reaction rule to be evaluated is being considered for biodegradation under aerobic conditions, in soil (moderate moisture) or water, at neutral pH, 25°C, with no competing or toxic other compounds. Assign a number to each rule using this scale:

  1. Highly likely reaction. This is to be reserved for reactions that will almost certainly occur and occur with the highest priority. For example, if an acid chloride is generated, these compounds almost invariably undergo spontaneous hydrolysis in water very rapidly. So this would likely occur as the next step in any metabolic pathway in any bacterium. UM-BBD btrule bt0026, Acid chloride -> Carboxylate is an example of this type of rule.

  2. Likely reaction. This is to be used when almost all bacteria can catalyze a given reaction with a functional group present in a molecule. For example, if the substrate has an ester linkage, it is often hydrolyzed by very common esterases, found both extracellularly and intracellularly. So giving an ester hydrolysis rule a score of 2 would give it a high priority but after an acid chloride hydrolysis reaction. You should also use 2 for a reaction that is significantly likely to occur once a certain intermediate has been generated. For example, aromatic ring cis-dihydrodiols are likely to be dehydrogenated to form catechols. Most organisms that make cis-dihydrodiols will also catalyze their dehydrogenation, thus the latter reaction is likely due to the linkage. UM-BBD btrule bt0255, Dihydrodihydroxyaromatic -> 1,2-Dihydroxyaromatic is an example of this type of rule.

  3. Possible reaction (neutral). This applies to reactions that are common but not certain to occur in every system. For example, hydrocarbon oxygenation reactions are quite possible, but may or may not be likely to occur depending on what the substrate is. These must be looked at individually. Some may be likely, some may be possible and some may be unlikely based on current knowledge (an example of the latter may be oxygenases that work on 5-ring polycyclic aromatic hydrocarbons). UM-BBD btrule bt0002, secondary Alcohol -> Ketone is an example of this type of rule.

  4. Unlikely reaction. This would be the case for reactions that clearly might occur, but are either very rarely catalyzed in bacterial and fungal populations, or that don't seem likely to occur because of the initial conditions we are using or other chemical/biochemical reason. UM-BBD btrule bt0094, Carboxylate + CoA -> CoA thioester, which is unlikely to occur under aerobic conditions, is an example of this type of rule.

  5. Highly unlikely reactions. These reactions are ones, for example, that have never been observed under aerobic conditions and the enzymes are oxygen sensitive. Thus, given our initial conditions, we would expect that these reactions are highly unlikely. UM-BBD btrule bt0270, Toluene -> Benzylsuccinate is an example of this type of rule.

  6. No decision. This is reserved for cases where you cannot assign a number for whatever reason.
Please try to assign as many numbers 1-5 as possible, and use 6 rarely. There is a place for qualifying comments at the bottom where you can discuss further any btrule that you think is unclear or difficult to prioritize.

On April 18, 2005, the UM-BBD contains 250 biotransformation descriptions for 240 biotransformation rules. All rules, and links to their btrule pages, are available below. The btrule pages include all UM-BBD reactions that exemplify the rule. Some reactions require up to three rules. The complete list is divided into five 50-rule subsets by blank lines; the subsets are also available separately.
List of all rules, Subset A, Subset B, Subset C, Subset D, Subset E. A few outliers still need attention: Outliers


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