Abstract: The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate, 1,4-butanediol, or other product pathway and being capable of producing 4-hydroxybutyrate, 1,4-butanediol, or other product, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate, 1,4-butanediol, or other product or related products using the microbial organisms.

Abstract: The invention provides non-naturally occurring microbial organisms containing an alkene pathway having at least one exogenous nucleic acid encoding an alkene pathway enzyme expressed in a sufficient amount to convert an alcohol to an alkene. The invention additionally provides methods of using such microbial organisms to produce an alkene, by culturing a non-naturally occurring microbial organism containing an alkene pathway as described herein under conditions and for a sufficient period of time to produce an alkene.

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: Provided herein are non-naturally occurring microbial organisms having a pathway for production of (3R)-hydroxybutyl (3R)-hydroxybutyrate, wherein the organism can further include a (R)-1,3-butanediol pathway, a (3R)-hydroxybutyrate pathway, a (3R)-hydroxybutyryl-CoA pathway, an acetoacetate pathway, an acetoacetyl-CoA pathway, a (3R)-hydroxybutyl-ACP pathway, or an acetoacetyl-ACP pathway. Additionally provided are methods and processes for producing and isolating (3R)-hydroxybutyl (3R)-hydroxybutyrate using the microbial organisms, and various compositions having the (3R)-hydroxybutyl (3R)-hydroxybutyrate. Still further provided are methods of treating or preventing a disease, disorder or condition using the (3R)-hydroxybutyl (3R)-hydroxybutyrate produced by the microbial organisms of the invention.

Abstract: The invention provides non-naturally occurring microbial organisms containing butadiene or 2,4-pentadienoate pathways comprising at least one exogenous nucleic acid encoding a butadiene or 2,4-pentadienoate pathway enzyme expressed in a sufficient amount to produce butadiene or 2,4-pentadienoate. The organism can further contain a hydrogen synthesis pathway. The invention additionally provides methods of using such microbial organisms to produce butadiene or 2,4-pentadienoate by culturing a non-naturally occurring microbial organism containing butadiene or 2,4-pentadienoate pathways as described herein under conditions and for a sufficient period of time to produce butadiene or 2,4-pentadienoate. Hydrogen can be produced together with the production of butadiene or 2,4-pentadienoate.

Abstract: Provided herein is a non-naturally occurring microbial organism having a 1,3-butanediol (1,3-BDO) pathway and comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In some embodiments, the pathway includes reducing equivalents from CO or hydrogen. In certain embodiments, a 1,3-BDO pathway proceeds by way of central metabolites pyruvate, succinate or alpha-ketoglutarate. Also provided herein is a method for producing 1,3-BDO, includes culturing such microbial organisms under conditions and for a sufficient period of time to produce 1,3-BDO.

Abstract: The invention provides non-naturally occurring microbial organisms containing caprolactone pathways having at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce caprolactone. The invention additionally provides methods of using such microbial organisms to produce caprolactone by culturing a non-naturally occurring microbial organism containing caprolactone pathways as described herein under conditions and for a sufficient period of time to produce caprolactone.

Abstract: Provided is a method of producing and isolating a diamine produced by microbial fermentation that minimizes undesirable salt formation to provide a lower cost process.

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ?-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB).

Abstract: Provided herein are lasso peptides libraries, and particularly phage display libraries of lasso peptides. Also provided herein are related methods and systems for producing the libraries and for screening the libraries to identify candidate lasso peptides having desirable properties.

Abstract: This invention relates to compounds and compositions useful as inhibitors of PIM kinases. Also provided are methods of synthesis and methods of use of PIM inhibitors in treating individuals suffering from cancerous malignancies.

Abstract: Provided herein are endothelin receptor antagonistic lasso peptides and related compositions and methods for the management, prevention and/or treatment of an endothelin B receptor (ETBR)-mediated proliferative disease, such as cancer. Biosynthetic methods for producing the lasso peptides are also provided. In some embodiments, the method comprises administering to the subject a therapeutic effective amount of a lasso peptide, wherein the lasso peptide comprises an amino acid sequence selected from SEQ ID NOS:1-17 and 42-56. In particular embodiments, the lasso peptide is GI-D9 cyclized.

Abstract: The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate or related products using the microbial organisms.

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: A non-naturally occurring eukaryotic or prokaryotic organism includes one or more gene disruptions occurring in genes encoding enzymes imparting increased fumarate, malate or acrylate production in the organism when the gene disruption reduces an activity of the enzyme. The one or more gene disruptions confers increased production of acrylate onto the organism. Organisms that produce acrylate have an acrylate pathway that at least one exogenous nucleic acid encoding an acrylate pathway enzyme expressed in a sufficient amount to produce acrylate, the acrylate pathway comprising a decarboxylase. Methods of producing fumarate, malate or acrylate include culturing these organisms.

Abstract: A non-naturally occurring microbial organism includes a microbial organism having a 1,3-butanediol (1,3-BDO) pathway having at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO.

Abstract: This disclosure relates to compounds and compositions useful as inhibitors of PIM kinases. Also provided are methods of synthesis and methods of use of PIM inhibitors in treating individuals suffering from cancerous malignancies.

Abstract: The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO.

Abstract: The invention provides non-naturally occurring microbial organisms containing butadiene or 2,4-pentadienoate pathways comprising at least one exogenous nucleic acid encoding a butadiene or 2,4-pentadienoate pathway enzyme expressed in a sufficient amount to produce butadiene or 2,4-pentadienoate. The organism can further contain a hydrogen synthesis pathway. The invention additionally provides methods of using such microbial organisms to produce butadiene or 2,4-pentadienoate by culturing a non-naturally occurring microbial organism containing butadiene or 2,4-pentadienoate pathways as described herein under conditions and for a sufficient period of time to produce butadiene or 2,4-pentadienoate. Hydrogen can be produced together with the production of butadiene or 2,4-pentadienoate.

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ?-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB).