The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme including the capability of reducing 5-((4S)-2-oxo-4-phenyl (1,3-oxazolidin-3-yl))-1-(4-fluorophenyl) pentane-1,5-dione to (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize the intermediate (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one in a process for making Ezetimibe.

The present invention is to provide a preparation of variant recombinant whole cell biocatalysts, referred herein as “designer cells” having significantly enhanced carbonyl reductase activity for use in the efficient production of variant industrially important enantiomerically enriched alcohols. More specifically, the alcohol is optically pure ethyl (S)-4-chloro-3-hydroxybutyrate, which is useful as chiral building block and an intermediate for the production of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors.

The present invention has its object to provide a novel polypeptide having amidase activity to selectively hydrolyze S-enantiomer in racemic nipecotamide, a DNA encoding the polypeptide, a vector containing the DNA, a transformant transformed with the vector, and a method for producing an optically active carboxylic acid amide and an optically active carboxylic acid in which a racemic carboxylic acid amide is hydrolyzed with the polypeptide or the transformant.

The present invention refers to a modified D-amino acid oxidase (DAAO). In particular, the modified DAAO of the present invention has the activity of catalyzing the oxidation of D-glufosinate into PPO. Further, the modified DAAO of the present invention has increased activity of catalyzing the oxidation of D-glufosinate into PPO and/or increased stability as compared to SEQ ID NO: 4. The present invention also refers to the polynucleotide encoding the modified DAAO of the present invention, the vector and host cell expressing the modified DAAO of the present invention, and the method of producing L-glufosinate with the modified DAAO and host cell of the present invention.

The present invention refers to a modified D-amino acid oxidase (DAAO). In particular, the modified DAAO of the present invention has the activity of catalyzing the oxidation of D-glufosinate into PPO. Further, the modified DAAO of the present invention has increased activity of catalyzing the oxidation of D-glufosinate into PPO and/or increased stability as compared to SEQ ID NO: 4. The present invention also refers to the polynucleotide encoding the modified DAAO of the present invention, the vector and host cell expressing the modified DAAO of the present invention, and the method of producing L-glufosinate with the modified DAAO and host cell of the present invention.

Disclosed are methods for producing optically active amino acids and amines. According to the methods, α-keto acids are generated as reaction intermediates, and as a result, ω-transaminase-catalyzed kinetic resolution of racemic amino acids or amines as racemic amine compounds enables the production of optically active amine compounds without the need to use expensive α-keto acids as starting materials. Therefore, the optically active amine compounds are produced at greatly reduced costs. In addition, the optically active amine compounds have high enantiomeric excess.

The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes.

The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes.

The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.

The present invention provides solid forms of compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, methods of producing the same, and methods of using the same in the treatment of ACC-mediated diseases.