title: 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.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, Czech Republic 142 20. ulanova@biomed.cas.cz
authors.forename: Dana
authors.initials: D
authors.lastname: Ulanova
authors.forename: Jitka
authors.initials: J
authors.lastname: Novotná
authors.forename: Yvona
authors.initials: Y
authors.lastname: Smutná
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kameník
authors.forename: Radek
authors.initials: R
authors.lastname: Gazák
authors.forename: Miroslav
authors.initials: M
authors.lastname: Sulc
authors.forename: Petr
authors.initials: P
authors.lastname: Sedmera
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kadlcík
authors.forename: Kamila
authors.initials: K
authors.lastname: Plhácková
authors.forename: Jirí
authors.initials: J
authors.lastname: Janata
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008034:Lincomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011392:Proline; D008034:Lincomycin