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Method for determining gene knockouts

Patent ·
OSTI ID:1084350

A method for determining candidates for gene deletions and additions using a model of a metabolic network associated with an organism, the model includes a plurality of metabolic reactions defining metabolite relationships, the method includes selecting a bioengineering objective for the organism, selecting at least one cellular objective, forming an optimization problem that couples the at least one cellular objective with the bioengineering objective, and solving the optimization problem to yield at least one candidate.

Research Organization:
The Penn State Research Foundation (University Park, PA)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG03-01ER25499
Assignee:
The Penn State Research Foundation (University Park, PA)
Patent Number(s):
8,457,941
Application Number:
13/210,484
OSTI ID:
1084350
Country of Publication:
United States
Language:
English

References (98)

Analysis and design of metabolic reaction networks via mixed-integer linear optimization journal May 1996
Optimization-based framework for inferring and testing hypothesized metabolic objective functions journal June 2003
Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimization journal October 2003
Exploring the overproduction of amino acids using the bilevel optimization framework OptKnock journal December 2003
Probing the performance limits of theEscherichia coli metabolic network subject to gene additions or deletions journal January 2001
Equations and calculations for fermentations of butyric acid bacteria journal February 1984
Equations and calculations of product yields and preferred pathways for butanediol and mixed-acid fermentations journal January 1985
Computer-aided synthesis of biochemical pathways journal December 1990
Optimization in integrated biochemical systems journal August 1992
Metabolic flux distributions inCorynebacterium glutamicum during growth and lysine overproduction journal March 1993
Stoichiometric analysis of animal cell growth and its application in medium design journal May 1994
Modification of central metabolic pathway inescherichia coli to reduce acetate accumulation by heterologous expression of thebacillus subtilis acetolactate synthase gene journal October 1994
Metabolic flux distributions in Penicillium chrysogenum during fed-batch cultivations: METABOLIC FLUX DISTRIBUTIONS IN PENICILLIUM CHRYSOGENUM journal April 1995
Metabolic Capabilities of Escherichia coli: I. Synthesis of Biosynthetic Precursors and Cofactors journal December 1993
Modeling DNA Mutation and Recombination for Directed Evolution Experiments journal August 2000
Regulation of Gene Expression in Flux Balance Models of Metabolism journal November 2001
Metabolic Flux Analysis ofEscherichia coliDeficient in the Acetate Production Pathway and Expressing theBacillus subtilisAcetolactate Synthase journal January 1999
Bulk Chemicals from Biotechnology: The Case of 1,3-Propanediol Production and the New Trends book January 2002
Hierarchical optimization: An introduction journal December 1992
Lagrangean relaxation for integer programming book January 1974
Study of two-stage processes for the microbial production of 1,3-propanediol from glucose journal October 2002
Biotechnology of succinic acid production and markets for derived industrial products journal May 1999
Microbial production of 1,3-propanediol journal September 1999
An estimation of minimal genome size required for life journal April 1995
Synthesis of biochemical production routes journal June 1992
Growth energetics and metabolic fluxes in continuous cultures of Penicillium chrysogenum journal February 1996
Biochemical systems analysis journal December 1969
Integrated approaches to the design of media and feeding strategies for fed-batch cultures of animal cells journal March 1997
Hydrogen production by biological processes: a survey of literature journal January 2001
Metabolic reconstruction using shortest paths journal April 2000
Mathematical models of metabolic pathways journal April 1999
Metabolic modeling of microbial strains in silico journal March 2001
Metabolic pathways in the post-genome era journal May 2003
Advances in flux balance analysis journal October 2003
Metabolic engineering for the microbial production of 1,3-propanediol journal October 2003
Gene Expression Profiling by DNA Microarrays and Metabolic Fluxes in Escherichia coli journal April 2000
Identifying rate-controlling enzymes in metabolic pathways without kinetic parameters journal January 1991
Minimal Reaction Sets for Escherichia coli Metabolism under Different Growth Requirements and Uptake Environments journal October 2001
Glycerol Production in a Triose Phosphate Isomerase Deficient Mutant of Saccharomyces cerevisiae journal October 1996
Metabolic Engineering of Propanediol Pathways journal February 1998
Toward Metabolic Phenomics: Analysis of Genomic Data Using Flux Balances journal June 1999
The challenges of in silico biology journal November 2000
In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data journal February 2001
Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth journal November 2002
A genome-based approach for the identification of essential bacterial genes journal September 1998
Cleaning up with genomics: applying molecular biology to bioremediation journal October 2003
Reconstruction of the central carbon metabolism of Aspergillus niger: Reconstruction of Aspergillus niger metabolism journal October 2003
The metabolic world of Escherichia coli is not small journal February 2004
Engineering Escherichia coli for efficient conversion of glucose to pyruvate journal February 2004
A modular minimal cell model: Purine and pyrimidine transport and metabolism journal April 2004
Predicting crossover generation in DNA shuffling journal March 2001
Creating multiple-crossover DNA libraries independent of sequence identity journal September 2001
Analysis of optimality in natural and perturbed metabolic networks journal November 2002
A minimal gene set for cellular life derived by comparison of complete bacterial genomes. journal September 1996
A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics journal February 1998
The underlying pathway structure of biochemical reaction networks journal April 1998
A hierarchical approach to protein molecular evolution journal March 1999
The Escherichia coli MG1655 in silico metabolic genotype: Its definition, characteristics, and capabilities journal May 2000
From Annotated Genomes to Metabolic Flux Models and Kinetic Parameter Fitting journal September 2003
Combining evidence using p-values: application to sequence homology searches journal February 1998
E-CELL: software environment for whole-cell simulation journal January 1999
FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps journal January 2003
PathMiner: predicting metabolic pathways by heuristic search journal September 2003
MPW: the Metabolic Pathways Database journal January 1998
Eco Cyc: Encyclopedia of Escherichia coli genes and metabolism journal January 1999
Genome-wide expression profiling in Escherichia coli K-12 journal October 1999
WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction journal January 2000
KEGG: Kyoto Encyclopedia of Genes and Genomes journal January 2000
The EcoCyc and MetaCyc databases journal January 2000
The TIGR Gene Indices: analysis of gene transcript sequences in highly sampled eukaryotic species journal January 2001
The EcoCyc Database journal January 2002
The University of Minnesota Biocatalysis/Biodegradation Database: post-genomic data mining journal January 2003
The KEGG resource for deciphering the genome journal January 2004
MetaCyc: a multiorganism database of metabolic pathways and enzymes journal January 2004
OptStrain: A computational framework for redesign of microbial production systems journal November 2004
Genome of Geobacter sulfurreducens: Metal Reduction in Subsurface Environments journal December 2003
GENOME SEQUENCING: Laboratory Workhorse Decoded journal September 1997
The Complete Genome Sequence of Escherichia coli K-12 journal September 1997
GENETICS:Ethical Considerations in Synthesizing a Minimal Genome journal December 1999
Global Transposon Mutagenesis and a Minimal Mycoplasma Genome journal December 1999
Electricity Production by Geobacter sulfurreducens Attached to Electrodes journal March 2003
Presence of Acetyl Coenzyme A (CoA) Carboxylase and Propionyl-CoA Carboxylase in Autotrophic Crenarchaeota and Indication for Operation of a 3-Hydroxypropionate Cycle in Autotrophic Carbon Fixation † journal January 1999
Poly- -Hydroxybutyrate Biosynthesis in the Facultative Methylotroph Methylobacterium extorquens AM1: Identification and Mutation of gap11, gap20, and phaR journal November 2002
Malonyl-Coenzyme A Reductase from Chloroflexus aurantiacus, a Key Enzyme of the 3-Hydroxypropionate Cycle for Autotrophic CO2 Fixation journal May 2002
Multiple Formate Dehydrogenase Enzymes in the Facultative Methylotroph Methylobacterium extorquens AM1 Are Dispensable for Growth on Methanol journal December 2003
Production of beta-carotene in Zymomonas mobilis and Agrobacterium tumefaciens by introduction of the biosynthesis genes from Erwinia uredovora. journal January 1991
Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. journal January 1994
Cadmium removal by a new strain of Pseudomonas aeruginosa in aerobic culture. journal January 1997
Production of succinic acid through overexpression of NAD(+)-dependent malic enzyme in an Escherichia coli mutant. journal January 1997
Modeling DNA shuffling conference January 1998
Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions journal July 2000
Predicting biological system objectives de novo from internal state measurements journal January 2008
Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis journal December 2003
An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) journal August 2003
The Lagrangian Relaxation Method for Solving Integer Programming Problems journal January 1981
Applications of Multiobjective Optimization in Chemical Engineering journal January 2000
Computer Program for Calculating the Melting Temperature of Degenerate Oligonucleotides Used in PCR or Hybridization journal June 1997
Studies on hydrogen production by continuous culture system of hydrogen-producing anaerobic bacteria journal September 1997

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