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In some embodiments, the ketoreductase polypeptide can further comprise a domain or region corresponding to residues 1-89 of the sequence formula of SEQ ID NO: 111, 112, or 139, where the domain or region can have one or more or at least all of the following features: residue corresponding to X7 is a constrained or non-polar residue, particularly histidine; and residue corresponding to X66 is an a
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