Abstract: The present invention is directed to a process for improving daunorubicin and doxorubicin production by means of a recombinant microorganism in which a gene of daunorubicin metabolism is mutated. The mutated gene is preferably dnrU and/or dnrX.
Type:
Grant
Filed:
January 14, 1999
Date of Patent:
April 3, 2001
Assignee:
Pharmacia & Upjohn, S.P.A.
Inventors:
Silvia Filippini, Natalia Lomovskaya, Leonid Fonstein, Anna Luisa Colombo, C. Richard Hutchinson, Sharee L. Otten, Umberto Breme
Abstract: A method for selecting amino acid residues is disclosed which upon replacement will give rise to an enzyme with an altered pH optimum. The method is specific for metalloenzymes which are inactivated at low pH due to the dissociation of the metal ions. The method is based on altering the pK.sub.a of the metal coordinating ligands or altering the K.sub.ass for the metal binding. New glucose isomerases with an altered pH optimum are provided according to this method. These altered properties enable starch degradation to be performed at lower pH values.