Fungal strains and use thereof in antibiotic production

• US 5,362,638 A
• Filed: 11/30/1992
• Issued: 11/08/1994
• Est. Priority Date: 02/10/1992
• Status: Expired due to Fees

• Current Assignee: Novopharm Limited (Teva Pharmaceutical Industries Limited)
• Original Assignee: Novopharm Limited (Teva Pharmaceutical Industries Limited)
• Inventors: Dahiya, Jagroop S.
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): PROUTY, REBECCA E
• Application Number:
  US07/985,498
• Time in Patent Office: 708 Days
• Field of Search: 435/125, 435/172.2, 435/172.3, 435/254, 435/913, 435/918, 435/254.3, 435/256.1, 935/52, 935/60, 935/68, 935/89, 935/90, 935/92, 935/93, 935/97, 935/109, 536/23.2, 536/23.74
• US Class Current: 435/125
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/80 for fungi
• CPC Class Codes: C12P 17/06 containing a six-membered hetero ring, e.g. fluorescein
• CPC Class Codes: C12P 7/42 Hydroxy-carboxylic acids
• CPC Class Codes: Y10S 435/913 Aspergillus
• CPC Class Codes: Y10S 435/918 Aspergillus oryzae

Abstract

Lovastatin is produced by a process of fermentation using a fungal transformant produced by introducing into a non-lovastatin expressing Aspergillus strain such as a strain of Aspergillus oryzae the DNA of a lovastatin-expressing strain of Aspergillus terreus .

Claims

1. A process of preparing lovastatin which comprises fermenting a nutrient medium with a transformed fungal microorganism of an Aspergillus strain naturally incapable of expressing lovastatin but which has been transformed to contain foreign DNA derived from a lovastatin-producing Aspergillus terreus species and coding for the enzymes capable of synthesizing lovastatin, and a selectable marker, and recovering the lovastatin from the nutrient medium.

2. The process of claim 1 wherein the Aspergillus strain naturally incapable of expressing lovastatin is a strain selected from the group of species consisting of A. oryzae, A. niger, A. nidulans and A. fumigalis.

3. The process of claim 2 wherein said Aspergillus strain is a strain of the species A. oryzae.

4. The process of claim 3 wherein the foreign DNA introduced into the transformant contains cycloheximide-resistance genes as selectable marker.

5. The process of claim 4 wherein the transformant is ATCC 741356.

6. The process of claim 5 including the additional step of lactonization of the hydroxyacid analog formed in the fermentation process to lovastatin.

7. Fungal transformants capable of expressing the enzymes for synthesizing lovastatin, said transformants being strains of an Aspergillus sp. naturally incapable of lovastatin expression but containing foreign DNA derived from a lovastatin producing Aspergillus terreus strain and containing genes coding for the enzymes capable of synthesizing lovastatin.

8. Fungal transformants according to claim 7 wherein the Aspergillus sp. is selected from the group consisting of A. oryzae, A. niger, A. nidulans and A. fumigalus.

9. Fungal transformants according to claim 8 wherein the Aspergillus sp. is A. oryzae.

10. Fungal transformants according to claim 9, and comprising the product of transfection of total DNA from said A. terreus strain into said A. oryzae strain.

11. The fungal transformant ATCC 74135.