Method for the Evolutionary Design of Biochemical Reaction Networks

Abstract

The present invention relates to methods for achieving an optimal function of a biochemical reaction network. The methods can be performed in silico using a reconstruction of a biochemical reaction network of a cell and iterative optimization procedures. The methods can further include laboratory culturing steps to confirm and possibly expand the determinations made using the in silico methods, and to produce a cultured cell, or population of cells, with optimal functions. The current invention includes computer systems and computer products including computer-readable program code for performing the in silico steps of the invention.

1 - 11 . (canceled) 
     
     
         12 . A method of constructing optimal functions of a substantially whole biochemical reaction network in a cell comprising:
 (a) providing a database including biochemical reactions in the network;   (b) using optimization methods to calculate the optimal properties of the network;   (c) receiving a user's selection for altering the reactions in the network and recomputing the optimal properties;   (d) repeating optimization until the desired property criterion is met;   (e) displaying the results of the optimization for constructing the genetic makeup of a cell so that it contains the biochemical reactions as result of the optimization information;   (f) culturing the cells constructed under the specified environment conditions; and   (g) cultivating the cells for a sufficient period of time so that the cells evolve to the desired optimal performance.   
     
     
         13 . The method of  claim 12 , wherein the biochemical network is a metabolic network. 
     
     
         14 . The method of  claim 12 , wherein the biochemical network is a regulatory network. 
     
     
         15 . The method of  claim 12 , wherein the cells are prokaryotic cells. 
     
     
         16 . The method of  claim 12 , wherein the cells are eukaryotic cells. 
     
     
         17 . The method of  claim 16 , wherein the eukaryotic cells are yeast, fungal cells, animal cells or cell lines. 
     
     
         18 . The method of  claim 12 , wherein the constructed genetic makeup of the cell comprises altering one or more genes in the cell. 
     
     
         19 . The method of  claim 18 , wherein altering comprises introduction of a gene or genes into the cell. 
     
     
         20 . The method of  claim 18 , wherein altering comprises modification of an endogenous gene or genes in the cell.