C12Y102/01024

HIGH YIELD ROUTE FOR THE PRODUCTION OF COMPOUNDS FROM RENEWABLE SOURCES
20220389433 · 2022-12-08 ·

Provided herein are methods, compositions, and non-naturally occurring microbial organism for preparing compounds such as α-butanol, butyric acid, succinic acid, 1,4-butanediol, 1-pentanol, pentanoic acid, glutaric acid, 1,5-pentanediol, 1-hexanol, hexanoic acid, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, ε-Caprolactone, 6-amino-hexanoic acid, ε-Caprolactam, hexamethylenediamine, linear fatty acids and linear fatty alcohols that are between 7-25 carbons long, linear alkanes and linear α-alkenes that are between 6-24 carbons long, sebacic acid and dodecanedioic acid comprising: a) converting a C.sub.N aldehyde and pyruvate to a C.sub.N+3 β-hydroxyketone intermediate through an aldol addition; and b) converting the C.sub.N+3 β-hydroxyketone intermediate to the compounds through enzymatic steps, or a combination of enzymatic and chemical steps.

COMPOSITIONS AND METHODS FOR TREATING SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY (SSADHD)

Provided herein are compositions and methods for treating succinic semialdehyde dehydrogenase deficiency (SSADHD). Compositions may include a gene encoding a functional succinic semialdehyde dehydrogenase (SSADH) enzyme, such as ALDH5A1, operably linked to a targeting vector. The functional SSADII enzyme is envisioned to lower the levels of circulating gamma-hydroxybutyric acid (GHB) and γ-aminobutyric acid (GABA). In some embodiments, combination therapies are envisioned, comprising administering to the subject therapeutically effective amounts of a combination of a composition comprising a gene encoding a functional SSADII enzyme operably linked to a targeting vector; one or more mTOR inhibitors; and a GABA-T inhibitor. Suitable mTOR inhibitors include rapamycin, while suitable GABA-T inhibitors include vigabatrin.

Genes and uses for plant improvement

Transgenic seed for crops with improved traits are provided by trait-improving recombinant DNA where plants grown from such transgenic seed exhibit one or more improved traits as compared to a control plant. Exemplary recombinant DNA expresses a succinate semialdehyde dehydrogenase.

COMPOSITIONS AND METHODS FOR TREATING SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY (SSADHD)

Provided herein are compositions and methods for treating succinic semialdehyde dehydrogenase deficiency (SSADHD). Compositions may include a gene encoding a functional succinic semialdehyde dehydrogenase (SSADH) enzyme, such as ALDH5A1, operably linked to a targeting vector. The functional SSADH enzyme is envisioned to lower the levels of circulating gamma-hydroxybutyric acid (GHB) and -aminobutyric acid (GABA). In some embodiments, combination therapies are envisioned, comprising administering to the subject therapeutically effective amounts of a combination of a composition comprising a gene encoding a functional SSADH enzyme operably linked to a targeting vector; one or more mTOR inhibitors; and a GABA-T inhibitor. Suitable mTOR inhibitors include rapamycin, while suitable GABA-T inhibitors include vigabatrin.

HIGH YIELD ROUTE FOR THE PRODUCTION OF 1, 6-HEXANEDIOL
20200255840 · 2020-08-13 ·

Provided herein are methods, compositions, and non-naturally occurring microbial organism for preparing compounds such as 1-butanol, butyric acid, succinic acid, 1,4-butanediol, 1-pentanol, pentanoic acid, glutaric acid, 1,5-pentanediol, 1-hexanol, hexanoic acid, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, -Caprolactone, 6-amino-hexanoic acid, -Caprolactam, hexamethylenediamine, linear fatty acids and linear fatty alcohols that are between 7-25 carbons long, linear alkanes and linear -alkenes that are between 6-24 carbons long, sebacic acid and dodecanedioic acid comprising: a) converting a C.sub.N aldehyde and pyruvate to a C.sub.N+3 -hydroxyketone intermediate through an aldol addition; and b) converting the C.sub.N+3 -hydroxyketone intermediate to the compounds through enzymatic steps, or a combination of enzymatic and chemical steps.

RECOMBINANT POLYPEPTIDE HAVING ACYL-COA COMPOUND REDUCING ACTIVITY

Provided are a recombinant polypeptide having an excellent acyl-CoA compound reducing activity, and a production method of an aliphatic compound using the recombinant polypeptide.

A recombinant polypeptide has (a) an amino acid sequence A having a sequence identity of 60% or higher, 65% or higher, 70% or higher, 75% or higher, 80% or higher, 85% or higher, 88% or higher, 90% or higher, 93% or higher, 95% or higher, 97% or higher, 98% or higher, or 99% or higher with an amino acid sequence set forth in SEQ ID NO: 1; (b) a substitution of at least one amino acid at a position corresponding to a substrate-binding site of a polypeptide having an amino acid sequence set forth in SEQ ID NO: 1 in the amino acid sequence A; and (c) a reducing activity R of converting CoA thioester of an acyl-CoA compound into an aldehyde group, in which the reducing activity R includes (c-1) a reducing activity R1 of converting adipyl-CoA into 5-formylpentanoic acid in one step; and (c-2) a reducing activity R2 of converting succinyl-CoA into succinic semialdehyde.

Genes and uses for plant improvement

Transgenic seed for crops with improved traits are provided by trait-improving recombinant DNA where plants grown from such transgenic seed exhibit one or more improved traits as compared to a control plant. Also provided are methods of making transgenic plants with recombinant DNA and the one or more improved traits and methods of using those plants.

NOVEL METHOD FOR PRODUCING POLY-4-HYDROXYBUTYRATE AND 1,4-BUTANEDIOL

The present disclosure relates to a novel method of producing poly-4-hydroxybutyrate and/or 1,4-butanediol, and a microorganism using a poly-4-hydroxybutyrate production pathway.

Production of 4,6-dihydroxy-2-oxo-hexanoic acid
12104160 · 2024-10-01 · ·

Provided herein are methods, compositions, and non-naturally occurring microbial organism for preparing compounds such as1-butanol, butyric acid, succinic acid, 1,4-butanediol, 1-pentanol, pentanoic acid, glutaric acid, 1,5-pentanediol, 1-hexanol, hexanoic acid, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, ?-Caprolactone, 6-amino-hexanoic acid, ?-Caprolactam, hexamethylenediamine, linear fatty acids and linear fatty alcohols that are between 7-25 carbons long, linear alkanes and linear ?-alkenes that are between 6-24 carbons long, sebacic acid and dodecanedioic acid comprising: a) converting a C.sub.N aldehyde and pyruvate to a C.sub.N+3 ?-hydroxyketone intermediate through an aldol addition; and b) converting the C.sub.N+3 ?-hydroxyketone intermediate to the compounds through enzymatic steps, or a combination of enzymatic and chemical steps.

Mutants having capability to produce 1, 4-butanediol and method for preparing 1, 4-butanediol using the same

A mutant capable of producing 1,4-butanediol and a method of preparing 1,4-butanediol using the same are provided. The mutant microorganism is prepared by introducing and amplifying genes encoding enzymes converting succinate into 4-hydroxybutyrate and 4-hydroxybutyrate into 1,4-butanediol in a microorganism capable of producing succinate. The method includes culturing the mutant in a medium containing carbohydrate and obtaining 1,4-butanediol from the culture. Thus, 1,4-butanediol, which is essential in chemical industry, can be prepared in a biological process.