Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci

0340856 - MBÚ 2010 RIV US eng J - Journal Article
Ulanová, Dana - Novotná, Jitka - Smutná, Yvona - Kameník, Zdeněk - Gažák, Radek - Šulc, Miroslav - Sedmera, Petr - Kadlčík, Stanislav - Plháčková, Kamila - Janata, Jiří
Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci.
Antimicrobial Agents and Chemotherapy. Roč. 54, č. 2 (2010), s. 927-930. ISSN 0066-4804. E-ISSN 1098-6596
R&D Projects: GA MŠMT 2B08064; GA AV ČR IAA500200810
Institutional research plan: CEZ:AV0Z50200510
Keywords : COAGULASE-NEGATIVE STAPHYLOCOCCI * ERYTHROMYCIN RESISTANCE * SUBSTRATE-SPECIFICITY
Subject RIV: EE - Microbiology, Virology
Impact factor: 4.672, year: 2010

The lincomycin biosynthetic gene lmbX was deleted in Streptomyces lincolnensis ATCC 25466 that led to abolition of lincomycin production. Complementation experiments proved the blockage in 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
Permanent Link: http://hdl.handle.net/11104/0184015