Abstract:
Provided herein is a non-naturally occurring microbial organism (NNOMO) having a methanol metabolic pathway (MMP) that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as succinate. Also provided herein are methods for using such an organism to produce succinate.
Abstract:
Provided herein is a non-naturally occurring microbial organism having a methanol metabolic pathway (MMP) that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as 1,4-butanediol (BDO). Also provided herein are methods for using such an organism to produce BDO.
Abstract:
The invention provides microbial organisms comprising a genetic modification, including one or more genetic modifications, conferring to the microbial organism an increased production of succinate relative to the microbial organism in the absence of the genetic modification. The microbial organism additionally comprises pathways for reductive TCA and/or CO dehydrogenase and/or H 2 hydrogenase.
Abstract:
The invention provides non-naturally occurring microbial organisms having an ethylene glycol pathway. The invention additionally provides methods of using such organisms to produce ethylene glycol.
Abstract:
The invention provides a non-naturally occurring microbial organism having n-propanol and isopropanol pathways, 1,4-butanediol (14-BDO) and isopropanol pathways, 1,3-butanediol (13- BDO) and isopropanol pathways or methylacrylic acid (MAA) and isopropanolpathways. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in each of the respective n-propanol, 14-BDO, 13-BDO or MAA and isopropanol pathways. The invention additionally provides a method for co-producing n-propanol and isopropanol, 14-BDO and isopropanol, 13-BDO and isopropanol or MAA and isopropanol. The method can include culturing an n-propanol and an isopropanol co-producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an n-propanol, an isopropanol, a 14-BDO, a 13-BDO and/or a MAA pathway enzyme in a sufficient amount to produce each of the respective products, under conditions and for a sufficient period of time to produce each of the respective products.
Abstract:
The invention provides a non-naturally occurring microbial organism having a 6- aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The invention additionally provides a method for producing 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid. The method can include culturing a 6-aminocaproic acid, caprolactam or hexametheylenediamine producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway enzyme in a sufficient amount to produce the respective product, under conditions and for a sufficient period of time to produce 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid.
Abstract:
The invention provides a non-naturally occurring microbial organism having a 2- hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a 2- hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway. The invention additionally provides a method for producing 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid. The method can include culturing a 2-hydroxyisobutyric acid, 3- hydroxyisobutyric acid or methacrylic acid producing microbial organism expressing at least one exogenous nucleic acid encoding a 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid pathway enzyme in a sufficient amount and culturing under conditions and for a sufficient period of time to produce 2-hydroxyisobutyric acid, 3-hydroxyisobutyric acid or methacrylic acid.
Abstract:
The invention provides a non-naturally occurring microbial organism having a microbial organism having at least one exogenous gene insertion and/or one or more gene disruptions that confer production of primary alcohols. A method for producing long chain alcohols includes culturing these non-naturally occurring microbial organisms.
Abstract:
In alternative embodiments, provided herein are transcription/ translation (TX-TL) systems and methods of using them for use as rapid prototyping platforms for the synthesis, modification and identification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites, from biosynthetic gene cluster pipelines. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the combinatorial biosynthesis of natural products (NPs), natural product analogs (NPAs) and secondary metabolites. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the rapid prototyping of complex biosynthetic pathways as a way to rapidly assess combinatorial and biosynthetic designs before moving to cellular hosts. In alternative embodiments, these exemplary TX-TL systems are multiplexed for high-throughput (HT) automation and for prototyping engineered platforms for the synthesis or modification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites analogs.
Abstract:
The invention provides non-natural microbial organisms containing enzymatic pathways and/or metabolic modifications for enhancing carbon flux through acetyl-CoA, or oxaloacetate and acetyl-CoA. Embodiments of the invention include microbial organisms having a pathway to acetyl-CoA and oxaloacetate that includes phosphoketolase (a PK pathway). The organisms also have either (i) a genetic modification that enhances the activity of the non-phosphotransferase system (non-PTS) for sugar uptake, and/or (ii) a genetic modification(s) to the organism's electron transport chain (ETC) that enhances efficiency of ATP production, that enhances availability of reducing equivalents or both. The microbial organisms can optionally include (iii) a genetic modification that maintains, attenuates, or eliminates the activity of a phosphotransferase system (PTS) for sugar uptake. The enhanced carbon flux through acetyl-CoA and oxaloacetate can be used for production of a bioderived compound, and the microbial organisms can further include a pathway capable of producing the bioderived compound.