Genomatica, Inc.

Intrexon Ceu, Inc.

University of California

Christophe H Schilling

Mark Joseph Burk

Anthony P Burgard

John D Trawick

Imandokht Famili

Priti Pharkya

Stephen J Van Dien

Renata Usaite Black

Markus W Covert

Bornhard O Palsson

Anthony Burgard

Imandohkt Famili

Mark Burk

The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, COand/or Hto acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or COand Hto acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, COand/or H, alone or in combination with methanol, to produce acetyl-CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.

Methods and organisms for utilizing synthesis gas or other gaseous carbon sources and methanol

The invention provides a method of producing acrylic acid. The method includes contacting fumaric acid with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylic acid per mole of fumaric acid. Also provided is an acrylate ester. The method includes contacting fumarate diester with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylate ester per mole of fumarate diester. An integrated process for process for producing acrylic acid or acrylate ester is provided which couples bioproduction of fumaric acid with metathesis transformation. An acrylic acid and an acrylate ester production also is provided.

Methods for the synthesis of olefins and derivatives

The invention relates to newly identified selectable marker systems, cells for use in a selectable marker system, and methods for using the selectable marker systems.

Methods of expressing products in mammalian cells

The invention provides models and methods useful for optimizing cell lines. The invention provides methods and computer readable medium or media containing such methods. Such a computer readable medium or media can comprise commands for carrying out a method of the invention. The methods of the invention can be utilized to model improved characteristics of a cell line, for example, improved product production, improved growth, improved culture characteristics, and the like.

Mammalian cell line models and related methods

Methods for synthesis of olefins and derivatives

Selectable markers and related methods

The invention provides a computer readable medium or media, having: (a) a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) a constraint set for said plurality of reactions for said first, second and third data structures, and (e) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells. The first, second and third data structures also can include a plurality of data structures. Additionally provided is a method for predicting a physiological function of a multicellular organism. The method includes: (a) providing a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) providing a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) providing a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) providing a constraint set for said plurality of reactions for said first, second and third data structures; (e) providing an objective function, and (f) determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells.

Multicellular metabolic models and methods

The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, COand/or Hto acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or COand Hto acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.

The invention provides a computer implemented process for constructing a scalable output network model of a bioparticle. The process includes computer implemented steps of: (a) accessing a database of network gene components including an annotated network set of open reading frames (ORFs) of a bioparticle genome; (b) forming a data structure associating the network gene components with network reaction components, the data structure establishing a data set specifying a network model of connectivity and flow of the network reaction components, and (c) transforming the data set into a mathematical description of reactant fluxes defining the network model of connectivity and flow, wherein the mathematical description defines a scalable output network model of a bioparticle.

Systems and methods for constructing genomic-based phenotypic models

The invention provides in silico models for determining the physiological function of human cells, including human skeletal muscle cells. The models include a data structure relating a plurality ofreactants to a plurality ofreactions, a constraint set for the plurality ofreactions, and commands for determining a distribution of flux through the reactions that is predictive of aphysiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. A regulatedreaction can be represented in a model of the invention by including a variable constraint for the regulated reaction. The invention further provides methods for making an in silicomodel and methods for determining aphysiological function using a model of the invention.

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San Diego, CA, United States of America

Christophe H Schilling