Abstract: The present disclosure describes biomimetic membrane compositions with specifically designed angstrom-scale pores, particularly the continuum of pore sizes between 3 and 10 ?. Further provided are methods of redesigning a protein pore for a desired pore size. The redesigned protein pores and biomimetic membranes based on these proteins provide high selectivity while maintaining high permeability and have many advantages over existing aquaporin-based membranes.

Abstract: The present invention describes a two-step computational procedure that both identifies the optimum overall stoichiometry of conversion, along with alternate co-reactant (or co-product) combinations, of a feedstock substrate to a biochemical product, and selects for (non-)native reactions accessed from a universal database to identify at least one stoichiometry-balanced minimal metabolic network, in terms of number of reactions or sum of the flux in the network, that maximize carbon or energy efficiency while satisfying thermodynamic feasibility requirements. A representation of the overall stoichiometry of conversion and the minimal metabolic network as designed can be stored.

Abstract: The engineering of a pathway converting CH4 to acetate and eventually to liquid fuels is disclosed. The engineered pathway involves an engineered reversal of the natural pathway for acetate conversion to CH4 by microbes and coupling the engineered pathway to existing and future technologies for microbial or chemical conversion of acetate to liquid fuels. In one aspect, methods for producing modified pathways and/or microbes are provided. In another aspect engineered microbes, including Methanosarcina acetivorans, that incorporate the engineered pathway are provided, which can mediate conversion of CH4 to acetate for ultimate conversion to liquid fuels. In a further aspect, specific modifications to the components of the pathway are provided.

Abstract: 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.

Abstract: A computer-assisted method for identifying functionalities to add to an organism-specific metabolic network to enable a desired biotransformation in a host includes accessing reactions from a universal database to provide stoichiometric balance, identifying at least one stoichiometrically balanced pathway at least partially based on the reactions and a substrate to minimize a number of non-native functionalities in the production host, and incorporating the at least one stoichiometrically balanced pathway into the host to provide the desired biotransformation. A representation of the metabolic network as modified can be stored.

Abstract: This invention relates to methods and systems for in silico or bioinformatic modeling of cellular metabolism. The invention includes methods and systems for modeling cellular metabolism of an organism, comprising constructing a flux balance analysis model, and applying constraints to the flux balance analysis model, the constraints selected from the set consisting of: qualitative kinetic information constraints, qualitative regulatory information constraints, and differential DNA microarray experimental data constraints. In addition, the present invention provides for computational procedures for solving metabolic problems.

Abstract: 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.

Abstract: 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.

Abstract: A computer-assisted method for identifying functionalities to add to an organism-specific metabolic network to enable a desired biotransformation in a host includes accessing reactions from a universal database to provide stoichiometric balance, identifying at least one stoichiometrically balanced pathway at least partially based on the reactions and a substrate to minimize a number of non-native functionalities in the production host, and incorporating the at least one stoichiometrically balanced pathway into the host to provide the desired biotransformation. A representation of the metabolic network as modified can be stored.

Abstract: A computer-assisted method for identifying functionalities to add to an organism-specific metabolic network to enable a desired biotransformation in a host includes accessing reactions from a universal database to provide stoichiometric balance, identifying at least one stoichiometrically balanced pathway at least partially based on the reactions and a substrate to minimize a number of non-native functionalities in the production host, and incorporating the at least one stoichiometrically balanced pathway into the host to provide the desired biotransformation. A representation of the metabolic network as modified can be stored.

Abstract: This invention relates to methods and systems for in silico or bioinformatic modeling of cellular metabolism. The invention includes methods and systems for modeling cellular metabolism of an organism, comprising constructing a flux balance analysis model, and applying constraints to the flux balance analysis model, the constraints selected from the set consisting of: qualitative kinetic information constraints, qualitative regulatory information constraints, and differential DNA microarray experimental data constraints. In addition, the present invention provides for computational procedures for solving metabolic problems.

Abstract: This invention relates to methods and systems for in silico or bioinformatic modeling of cellular metabolism. The invention includes methods and systems for modeling cellular metabolism of an organism, comprising constructing a flux balance analysis model, and applying constraints to the flux balance analysis model, the constraints selected from the set consisting of: qualitative kinetic information constraints, qualitative regulatory information constraints, and differential DNA microarray experimental data constraints. In addition, the present invention provides for computational procedures for solving metabolic problems.

Abstract: 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.

Abstract: A modeling framework for predicting the number, type, and distribution of crossovers in directed evolution experiments is disclosed. The framework provides for determining how fragmentation length, annealing temperature, sequence identity, and number of shuffled parent sequences affect the number, type, and distribution of crossovers along the length of reassembled sequences. This framework allows for the optimization of directed evolution protocols in response to a particular enzyme or protein design challenge. One method according to the present invention includes applying equilibrium thermodynamics to a plurality of sequences to determine statistics of hybridization; and parameterizing an assembly algorithm using the statistics of hybridization.

Abstract: This invention relates to methods and systems for in silico or bioinformatic modeling of cellular metabolism. The invention includes methods and systems for modeling cellular metabolism of an organism, comprising constructing a flux balance analysis model, and applying constraints to the flux balance analysis model, the constraints selected from the set consisting of: qualitative kinetic information constraints, qualitative regulatory information constraints, and differential DNA microarray experimental data constraints. In addition, the present invention provides for computational procedures for solving metabolic problems.