Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Patent
1988-03-28
1991-11-05
Schwartz, Richard A.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
435 691, 435 712, 435 91, 435119, 435169, 4351721, 4351723, 43525235, 4353201, 435886, 435 74, 536 71, 536 27, 935 6, 935 14, 935 22, 935 29, 935 38, 935 39, 935 40, 935 42, 935 59, 935 60, 935 61, 935 75, C12N 121, C12N 1552, C12N 1576, C12P 1962
Patent
active
050631551
ABSTRACT:
The present invention discloses a method for producing a novel antibiotic, 2"'-O-demethyltylosin. The novel antibiotic, utilizing recombinant DNA technology, can be produced from a transformed mutant of a tylosin producing microorganism. By transforming for example Streptomyces fradiae GS 16 with plasmid pHJL284, the transformant can produce 2"'-O-demethyltylosin. Streytomyces fradiae GS16 is a tylosin producing species that contain a mutation in the tylE gene found in the tylosin biosynthetic pathway. The tylE gene codes for demethylmacrocin 2"'-O-methyltransferase enzyme (DMOMT), the enzyme that methylates the 2-hydroxyl position of the 6-deoxyallose moiety. Plasmid pHJL284 contains the cloned tylF gene which codes for the macrocin 3"'-O-methyltransferase enzxyme (MOMT), the enzyme that methylates the 3"'-hydroxyl position, but it does not contain the tylE gene. Transformation of S. fradiae GS16 with plasmid pHJL284 results in increased copies of the tylF gene in the absence of the tylE gene, therefore allowing an increased rate of methylation of the 3"'-hydroxyl position in the absence of the methyl group at the 2"'-hydroxyl position. The resulting transformant, therefore, can produce 2"'-O-demethyltylosin in appreciable quantities. The present invention is not limited to S. fradiae.For example, two other tylosin producing species such as Streptomyces rimosus and Streptomyces hygroscopicus, may also be used for purposes of the invention disclosed. 2"'-O-Demethyltylosin is useful as an antibiotic with a microbial inhibitory activity similar to tylosin.
REFERENCES:
Chater et al., 1985, Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered, The EMBO Journal, 4(7): 1893-1897.
Biological Abstracts Database Abstract No. 85046796; S. E. Fishman et al.: "Cloning genes for the biosynthesis of a macrolide antibiotic" & Proc. Natl. Acad. Sci. USA 1987, vol. 84, No. 23, pp. 8248-8252, *abstract* .
Biological Abstracts Database Abstract No. 76017914; H. A. Kirst et al. "Structure activity studies among 16 membered macrolide antibiotics related to tylosin" & J. of Antibiotics 1982, vol. 35, No. 12, pp. 1675-1682, *abstract* .
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Cox Karen L.
Seno Eugene T.
Wild Gene M.
Eli Lilly and Company
Harrison Nancy J.
Peet Richard C.
Schwartz Richard A.
Whitaker Leroy
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