Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, Czech Republic 142 20.
Antimicrob Agents Chemother. 2010 Feb;54(2):927-30. doi: 10.1128/AAC.00918-09. Epub 2009 Nov 16.
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.
林可霉素生物合成基因 lmbX 在林肯链霉菌 ATCC 25466 中被删除,该基因的缺失导致林可霉素的生产被废除。互补实验的结果证明了林可霉素前体 4-丙基-L-脯氨酸生物合成的阻断。用前体衍生物喂养该突变株,导致 4'-丁基-4'-去丙基林可霉素和 4'-戊基-4'-去丙基林可霉素高产,且没有林可霉素污染。此外,4'-戊基-4'-去丙基林可霉素对携带低水平林可酰胺类耐药基因的临床分离株的活性比林可霉素更强。