Merck + Co., Inc.

Carolyn L Ruby

Byron H Arison

Douglas J MacNeil

Stanley L Streicher

Philip S Paress

Tanya MacNeil

Susan J Danis

Christine C Chung

Keith M Gewain

Described is a new process for producing the immunosuppressant, L-682,993, a C-31 demethylated derivative of L-679,934 (FK-506), produced under fermentation conditions utilizing the new mutant microorganism Streptomyces sp. (Merck Culture Collection MA 7017) ATCC No. 55334, being a blocked second generation mutant of Streptomyces sp. (MA 6858) ATCC No. 55098. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Process for producing immunosuppressant agent

Described is a new process for producing the immunosuppressant, L-683,742, a C-31 demethylated, derivative of L-683,590 (FK-520), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Process for producing immunosuppressant agent L-683942 by fermentation

There are disclosed plasmids containing DNA isolated from Streptomyces avermitilis, the microorganism which is used to prepare avermectin compounds, identified as pAT1, pVE650 pVE855, pVE859, pVE1446, pVE923, and pVE924 which contain the genetic information for the biosynthesis of the avermectins. Methods for the isolation of such plasmid and for the manipulation of the plasmids to alter the formation of the avermectin compound are also disclosed.

Cloning genes from Streptomyces avermitilis for avermectin biosynthesis

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Montclair, NJ, United States of America

Carolyn L Ruby