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Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci.

ABSTRACT: The lincomycin biosynthetic gene lmbX was deleted in Streptomyces lincolnensis ATCC 25466, and deletion of this gene led to abolition of lincomycin production. The results of complementation experiments proved the blockage in the biosynthesis of lincomycin precursor 4-propyl-L-proline. Feeding this mutant strain with precursor derivatives resulted in production of 4'-butyl-4'-depropyllincomycin and 4'-pentyl-4'-depropyllincomycin in high titers and without lincomycin contamination. Moreover, 4'-pentyl-4'-depropyllincomycin was found to be more active than lincomycin against clinical Staphylococcus isolates with genes determining low-level lincosamide resistance.

SUBMITTER: Ulanova D

PROVIDER: S-EPMC2812159 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci.

Ulanova Dana D Novotná Jitka J Smutná Yvona Y Kameník Zdenek Z Gazák Radek R Sulc Miroslav M Sedmera Petr P Kadlcík Stanislav S Plhácková Kamila K Janata Jirí J

Antimicrobial agents and chemotherapy 20091116 2

The lincomycin biosynthetic gene lmbX was deleted in Streptomyces lincolnensis ATCC 25466, and deletion of this gene led to abolition of lincomycin production. The results of complementation experiments proved the blockage in the biosynthesis of lincomycin precursor 4-propyl-L-proline. Feeding this mutant strain with precursor derivatives resulted in production of 4'-butyl-4'-depropyllincomycin and 4'-pentyl-4'-depropyllincomycin in high titers and without lincomycin contamination. Moreover, 4'- ...[more]

PMID: 19917754

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