METHOD FOR THE EVOLUTIONARY DESIGN OF BIOCHEMICAL REACTION NETWORKS

• US 20080176327A1
• Filed: 10/29/2007
• Published: 07/24/2008
• Est. Priority Date: 01/31/2001
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Palsson, Bernhard O., Edwards, Jeremy S.
• Application Number:
  US11/927,254
• Publication Number:
  US 20080176327A1
• Time in Patent Office: Days
• US Class Current: 435/375
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic 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.

Claims

1. A method for optimizing a function of a biochemical reaction network in a cell comprising:

(a) calculating optimal properties of a biochemical reaction network by applying a computational optimization method to a list of reactions representing said biochemical reaction network;

(b) altering one or more reactions in said list of reactions in the biochemical reaction network and re-computing the optimal properties;

(c) repeating (b) until an optimized function is reached;

(d) constructing the genetic makeup of a cell to contain the biochemical reactions which result from (c);

(e) placing the cells constructed under (d) in culture under a specified environment, and

(f) cultivating the cells as in step (e) for a sufficient period of time and under conditions to allow the cells to evolve to the optimized function determined under (c), wherein the biochemical reaction network comprises a comprehensive biochemical reaction network.

2. The method of claim 1, wherein the biochemical network is a metabolic network.

3. The method of claim 1, wherein the biochemical network is a regulatory network.

4. The method of claim 2, wherein the cells are prokaryotic cells.

5. The method of claim 2, wherein the cells are eukaryotic cells.

6. The method of claim 1, wherein the eukaryotic cells are yeast, fungal cells, animal cells or cell lines.

7. The method of claim 1, wherein step (d) comprises altering one or more genes in the eukaryotic cell.

8. The method of claim 7, wherein altering comprises introduction of a gene or genes into the eukaryotic cell.

9. The method of claim 7, wherein altering comprises modification of an endogenous gene or genes in the eukaryotic cell.

10. The method of claim 1, wherein the biochemical reaction network comprises a substantially whole biochemical reaction network.

11. A method for optimizing production of a biochemical, comprising:

(a) calculating optimal properties of a biochemical reaction network for production of a biochemical by applying a computational optimization method to a list of reactions representing said biochemical reaction network;

(b) altering one or more reactions in said list of reactions in the biochemical reaction network and re-computing the optimal properties;

(c) repeating (b) until an optimized function for production of said biochemical is reached;

(d) constructing the genetic makeup of a eukaryotic cell to contain the biochemical reactions which result from (c);

(e) placing the cells constructed under (d) in culture under a specified environment, and

(f) cultivating the cells as in step (e) for a sufficient period of time and under conditions to allow the cells to evolve to the optimized function determined under (c), wherein said cells produce said desired biochemical.

12. The method of claim 11, wherein the biochemical network is a metabolic network.

13. The method of claim 11, wherein the biochemical network is a regulatory network.

14. The method of claim 12, wherein the cells are prokaryotic cells.

15. The method of claim 12, wherein the cells are eukaryotic cells.

16. The method of claim 11, wherein the eukaryotic cells are yeast, fungal cells, animal cells or cell lines.

17. The method of claim 11, wherein step (d) comprises altering one or more genes in the eukaryotic cell.

18. The method of claim 17, wherein altering comprises introduction of a gene or genes into the eukaryotic cell.

19. The method of claim 17, wherein altering comprises modification of an endogenous gene or genes in the eukaryotic cell.

20. The method of claim 11, wherein the biochemical reaction network comprises a substantially whole biochemical reaction network.