The present invention relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to ()-2-[(R)-(diphenylmethyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.

Disclosed herein is Candida parapsilosis CGMCC 9630, the carbonyl reductase expressed by said strain and the encoding gene and amino acid sequence thereof, the recombinant expression vector and recombinant expression transformant containing said gene sequence, and use of whole cells of Candida parapsilosis, carbonyl reductase or corresponding recombinant transformant thereof as catalyst in catalyzing asymmetric reduction of prochiral carbonyl compounds, particularly reduction of 6-carbonyl-8-halogenocaprylate to prepare the synthetic precursor of (R)--lipoic acid, (R)-6-hydroxy-8-halogenocaprylate. In comparison to other methods of asymmetric reduction for preparing (R)-6-hydroxy-8-halogenocaprylate, the disclosure has advantages of high substrate concentration, mild reaction conditions, environmental friendship, high yield, and high optical purity of the product, and thus has good prospect in industrial production of (R)---lipoic acid.

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 relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to ()-2-[(R)-(diphenylmethyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.

A method of epimerizing an (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid is provided. The method comprises contacting the (S)-1-benzylisoquinoline alkaloid with at least one enzyme. Contacting the (S)-1-benzyl-isoquinoline alkaloid with the at least one enzyme converts the (S)-1-benzylisoquinoline alkaloid to an (R)-1-benzylisoquinoline alkaloid.

Provided are: a protein complex capable of selectively and asymmetrically oxidizing an enantiomer of a secondary alcohol without adding a coenzyme and having an asymmetric oxidation activity in a water-soluble solvent system in the presence of oxygen; a method for producing the same; and a method for coating the protein complex with a high molecular weight compound. The method for producing the protein complex includes: (1) enclosing a crude water-soluble protein in a gel, air-oxidizing the gel, and eluting the protein complex into an aqueous solution; and (2) applying gravity to concentrate and precipitate the protein complex, redissolving the precipitate in an aqueous glycine sodium hydroxide solution of about 0.5 mM and allowing the same to homogeneously coexist with a high molecular weight compound, and re-precipitating the solution and dehydrating and drying the same to yield a protein complex coated with a high molecular weight compound.

The present disclosure relates to biocatalysts and its uses for the efficient preparation of eslicarbazepine, eslicarbazepine acetate, and analogs thereof.

The present invention provides a process for industrial production of chiral-1,1-difluoro-2-propanol. More specifically, a microorganism having the activity to cause asymmetric reduction of 1,1-difluoroacetone or an enzyme having the same activity is allowed to act on 1,1-difluoroacetone, whereby chiral-1,1-difluoro-2-propanol can be produced with high optical purity and in good yield. The process for production of the present invention is easy for industrial implementation.

The present invention relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to ()-2-[(R)-(diphenylmethyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.

A process for the production of furan derivatives from D-glucose, wherein A) D-glucose is converted into D-fructose in an enzymatic process, wherein redox cofactors are used and regenerated, whereby, as a result of at least two further enzymatically catalyzed redox reactions proceeding in the same reaction batch, one of the two redox cofactors accumulates in its reduced form and, respectively, the other one in its oxidized form, whereby D-glucose is converted into D-fructose, involving two or more oxidoreductases, and B) D-fructose is converted into furan derivatives,
and the use of furan derivatives produced in this manner.