Pharmacia & Upjohn

Farmitalia Carlo Erba S.r.l.

Pharmacia Corporation

Anna Luisa Colombo

Umberto Breme

Charles Richard Hutchinson

Silvia Filippini

Sharee L Otten

Leonid Fonstein

Claudio Scotti

Francesca Torti

Luisa Garofano

Natalia Lomovskaya

C Richard Hutchinson

Augusto Solari Inventi

Krishna M Madduri

Marina Ciomei

Giuliano Franchi

Marinella Caruso

Guiseppe Zanella

Natasha Lomovskaya

Giuliano Oronzo

Marco Tat&oacute;

Cinzia Portello

Emanuele Arlandini

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.

Process for preparing doxorubicin

Anthracycline glycosides

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 involved in the glycosylation of daunorubicin to acid-sensitive, baumycin-like compounds is inactivated.

Process for preparing daunorubicin and doxorubicin

The present invention concerns a process for improving doxorubicin production by means of a recombinant Streptomyces peucetius strain bearing a mutation in the gene dnrU coding for a protein involved in the metabolism of daunorubicin.

The ability to convert daunorubicin to doxorubicin can be conferred on a host cell by transformation with a recombinant vector comprising DNA encoding daunorubicin 14-hydroxylase. The host cell can then be used to produce doxorubicin.

Daunorubin 14-hydroxylase

DNA encoding daunorubicin 14-hyroxylase and method for preparing

Doxorubicin resistance can be conferred on a host by transforming the host with a recombinant vector comprising a DNA having the configuration of restriction sites shown in FIGS. 1 or 2 of the accompanying drawings or a restriction fragment derived therefrom containing a gene coding for doxorubicin resistance.

Isolation and characterisation of genes resistant to anthracycline

The ability to improve the conversion of .epsilon.-rhodomycinone to daunorubicin can be conferred on a bacterial host transformed with a recombinant vector comprising a DNA coding for an appropriate protein useful for that conversion. Furthermore, the bacterial host may have a mutation that blocks the function of a gene of daunorubicin metabolism.

Process for preparing daunorubicin

The ability to convert carminomycin to daunorubicin can be conferred on a host by transforming the host with a recombinant vector comprising a DNA having the configuration of restriction sites shown in FIGS. 2, 3 and 4 and a nucleotide sequence shown in FIG. 3 of the accompanying drawings or a restriction fragment derived therefrom containing a gene coding for carminomycin 4-O-methyltransferase.

The ability to convert carminomycin to daunorubicin can be conferred on a host by transforming the host with a recombinant vector comprising a DNA having the configuration of restriction sites shown in FIGS. 2, 3 & 4 and nucleotide sequence shown in FIG. 3 of the accompanying drawings or a restriction fragment derived therefrom containing a gene coding for carminomycin 4-O-methyltransferase.

Growing community of inventors

Milan, Italy

Anna Luisa Colombo