Among other things, the present disclosure provides biosynthesis polypeptides, methods, and non-naturally occurring microbial organisms for preparing various compounds such as 1,5-pentanediol, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, and 2-keto carboxylic acids.

The present invention relates to methods for the preparation of α-hydroxyacyl compounds, and peptides for the catalyzed formation of α-hydroxyacyl compounds as well as their use in the preparation of α-hydroxyacyl compounds.

The present disclosure provides thiolases and polypeptide variants of 3-hydroxybutyryl-CoA dehydrogenase, nucleic acids encoding the same, vectors comprising the nucleic acids, and cells comprising the polypeptide variants and/or thiolase, the nucleic acids, and/or the vectors. The present disclosure also provides methods of making and using the same, including methods for culturing cells, and for the production of various products, including 3-hydroxybutyryl-CoA (3-HB-CoA), 3-hydroxybutyraldehyde (3-HBal), 3-hydroxybutyrate (3-HB), 1,3-butanediol (1,3-BDO), and esters and amides thereof, and products made from any of these.

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.

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.

Provided is an enzymatic process for preparing mercaptans from disulfides.

Provided is an enzymatic process for preparing mercaptans from disulfides.

Provided is a method for producing L-methionine in which O-phospho-L-homoserine and methanethiol are enzymatically converted into L-methionine and H3PO4. Such a conversion is achieved by an enzyme called O-phospho-L-homoserine (OHPS) dependent methionine synthase. Also described are O-phospho-L-homoserine (OHPS) dependent methionine synthases, i.e. proteins which are able to enzymatically convert O-phospho-L-homoserine and methanethiol into L-methionine and H3PO4 as well as microorganisms which have been genetically modified so as to be able to produce L-methionine from O-phospho-L-homoserine and methanethiol. Furthermore described are methods to screen for enzymes that catalyze the conversion of O-phospho-L-homoserine and methanethiol into L-methionine and H.sub.3PO.sub.4.

Provided is a method for producing L-methionine in which O-phospho-L-homoserine and methanethiol are enzymatically converted into L-methionine and H3PO4. Such a conversion is achieved by an enzyme called O-phospho-L-homoserine (OHPS) dependent methionine synthase. Also described are O-phospho-L-homoserine (OHPS) dependent methionine synthases, i.e. proteins which are able to enzymatically convert O-phospho-L-homoserine and methanethiol into L-methionine and H3PO4 as well as microorganisms which have been genetically modified so as to be able to produce L-methionine from O-phospho-L-homoserine and methanethiol. Furthermore described are methods to screen for enzymes that catalyze the conversion of O-phospho-L-homoserine and methanethiol into L-methionine and H.sub.3PO.sub.4.

The present disclosure concerns the large-scale manufacture of pharmaceutical compounds, and novel intermediates for use in the manufacture. International Patent Application WO2011154737 discloses morpholine pyrimidines useful for treating cancer, processes for their preparation and pharmaceutical compositions thereof. In particular, WO2011154737 discloses, as experimental Example 2.02 on page 60, the compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)—S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (hereafter referred to as the compound of Formula (I)). The structure of the compound of Formula (I) is shown below. A synthetic route to the compound of Formula (I) is described at pages 51 to 57, 66 and 67 of WO2011154737, and is summarised below in Scheme 1.

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