Selective inhibition of enzyme synthesis by lincomycin …

23/11/2017 · Chemical synthesis and structural study of lincomycin ..

Buy and view Lincomycin HCl, USP, 7179-49-9, MSDS

The aminoglycosides are products of species and are represented by streptomycin, kanamycin,tobramycin and gentamicin. These antibiotics exert theiractivity by binding to bacterial ribosomes and preventing theinitiation of protein synthesis.

Lincomycin stimulates synthesis of TEM-2 beta ..

Streptomycin binds to 30S subunit of the bacterial ribosome,specifically to the S12 protein which is involved in the initiation ofprotein synthesis. Experimentally, streptomycin has been shown toprevent the initiation of protein synthesis by blocking the binding ofinitiator N-formylmethionine tRNA to the ribosome. It also prevents thenormal dissociation of ribosomes into their subunits, leaving themmainly in their 70S form and preventing the formation of polysomes. Theoverall effect of streptomycin seems tobe one of distorting the ribosome so that it no longer can carry outitsnormal functions. This evidently accounts for its antibacterialactivitybut does not explain its bactericidal effects, which distinguishesstreptomycinand other aminoglycosides from most other protein synthesis inhibitors.

Lincomycin A is a potent antimicrobial agent noted for its unusual C1 methylmercapto-substituted 8-carbon sugar. Despite its long clinical history for the treatment of Gram-positive infections, the biosynthesis of the C8-sugar, methylthiolincosamide (MTL), is poorly understood. Here, we report our studies of the two initial enzymatic steps in the MTL biosynthetic pathway leading to the identification of ----octose 8-phosphate as a key intermediate. Our experiments demonstrate that this intermediate is formed via a transaldol reaction catalyzed by LmbR using -fructose 6-phosphate or -sedoheptulose 7-phosphate as the C3 donor and -ribose 5-phosphate as the C5 acceptor. Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C8-sugar (octulose 8-phosphate) to octose 8-phosphate. These results provide, for the first time, evidence for the biosynthetic origin of the C8 backbone of MTL.