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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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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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