Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci.
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.
Ulanova
Dana
D
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, Czech Republic 142 20. ulanova@biomed.cas.cz
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
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*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011392:Proline; D008034:Lincomycin