US 8,288,141 B2 · Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine

Abstract

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 engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Claims23

Dependent claims

A ketoreductase polypeptide, wherein the polypeptide has an amino acid sequence that is at least 90% identical to a reference sequence of SEQ ID NO:2 and has at least the following features:

(a) the residue corresponding to residue X94 is aspartic acid, (b) the residue corresponding to residue X145 is phenylalanine;
and (c) the residue corresponding to residue X190 is proline.

Dependencies are inferred from the claim text.

Facts

Application

12/549,293Filed 27 Aug 2009 · us provisional application

Priority

27 Aug 2008

Published

US 2010/0173369 A18 Jul 2010

Granted

16 Oct 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C12P 17/00
Preparation of heterocyclic carbon compounds with only o, n, s, se or
C12N 9/0006
Oxidoreductases: acting on CH-OH groups as donors
C12P 13/001
Preparation of nitrogen-containing organic compounds: amines; Imines
C12Y 101/01164
With NAD+ or NADP+ as acceptor: hexadecanol dehydrogenase

Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine

Life of this patent

Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine

Life of this patent

Abstract

Claims23