BioNetGen - Software to Discover Novel Biotransformations
INVENTION: This software solution has been extensively used at Northwestern to identify novel reaction pathways. This offers an opportunity to look for ways to produce materials from renewable resources, such as plants and crops, or to produce novel products.ADVANTAGES: There have been other attempts to identify novel reaction pathways. However, these competing methods require users to specify known enzymes and targeted reaction products, as well as known metabolic intermediates. In this sense, competing methods are limited in terms of the novel pathways they can discover.
In contrast, the software solution invented at Northwestern:
Identifies novel products. Identifies possible "modes" of enzymatic action (enzyme characteristics) so that novel enzymes can be identified. Applies reaction rules to automatically generate and "discover" novel pathways, reactants and products. Applies termination criteria to identify feasible reactions and exclude infeasible ones. Estimates thermodynamic properties of reactions. This further qualifies reaction feasibility. Provides data from which to calculate reaction yields. The software specifies a set of molecules and paths connecting them based on likely enzyme-catalyzed transformations. This information alone can be used to explore many "what if" scenarios. What new pathways exist for producing a particular molecule from a given starting material? What new molecules can be produced given a set of known biochemical reaction types? What family of enzymes should be investigated in more detail given a desired conversion route between molecules? Beyond these more qualitative questions, it is important to analyze the generated mechanism quantitatively and evaluate its energetic feasibility. The energetic feasibility of a reaction step or pathway can be evaluated if the thermodynamic properties of the participating species are known. However, for most of the biological molecules such knowledge is lacking especially when one considers these compounds in a non- ideal intracellular environment. Moreover, one of the outputs of the software solution will be the generation of novel compounds for which there will be no information about their thermodynamic properties. To overcome this limitation, the software applies quantum mechanics and/or other means to derive thermodynamic properties.
For more details on this invention, see publication Bioinformatics. 2005 Apr 15;21(8):1603-9. Epub 2004 Dec 21.
FIELD OF APPLICATION: Renewable natural resources; industrial catalysis; rational drug design; chemical and enzymatic database construction.
STAGE OF DEVELOPMENT AND IMPLEMENTATION: BioNetGen has been applied to analyze aromatic amino acid pathways, and has discovered almost 75,000 novel biochemical routes from chorismate to phenylalanine, more than 350,000 from chorismate to tyrosine, but only 13 from chorismate to tryptophan. Analysis further suggests that the native pathways are thermodynamically more favorable than the possible alternative pathways. BioNetGen has determined which enzyme class contributes to a novel pathway, and some compounds identified by BioNetGen already exist in biological and chemical databases. The software is at the point where it could be implemented to screen through databases of enzymes to identify those that could be used as starting points for new pathways. We are happy to provide you with a product demonstration.
Northwestern seeks a licensing partner to commercialize this software. A patent application has been filed.
Inventor(s): Vassily Hatzimanikatis, Linda J. Broadbelt, Chunhui Li, Justin Ionita
Type of Offer: Licensing
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