biostudies-literatureSasaki ENIGMS NIH HHS17432-5https://www.ebi.ac.uk/biostudies/studies/S-EPMC3486926biostudies-literatureUnknown134(42)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 C(8)-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 D-erythro-D-gluco-octose 8-phosphate as a key intermediate. Our experiments demonstrate that this intermediate is formed via a transaldol reaction catalyzed by LmbR using D-fructose 6-phosphate or D-sedoheptulose 7-phosphate as the C(3) donor and D-ribose 5-phosphate as the C(5) acceptor. Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C(8)-sugar (octulose 8-pJournal of the American Chemical SocietyConstruction of the octose 8-phosphate intermediate in lincomycin A biosynthesis: characterization of the reactions catalyzed by LmbR and LmbN.PMC3486926GM035906R37 GM035906R01 GM035906Lin KYLiu HWSasaki ELin CIfalseConstruction of the octose 8-phosphate intermediate in lincomycin A biosynthesis: characterization of the reactions catalyzed by LmbR and LmbN.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 C(8)-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 D-erythro-D-gluco-octose 8-phosphate as a key intermediate. Our experiments demonstrate that this intermediate is formed via a transaldol reaction catalyzed by LmbR using D-fructose 6-phosphate or D-sedoheptulose 7-phosphate as the C(3) donor and D-ribose 5-phosphate as the C(5) acceptor. Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C(8)-sugar (octulose 8-p2012-01-01T00:00:00Z2012 Oct2025-04-04T20:28:31.975Z2019-03-26T23:30:00ZS-EPMC34869262298931010.1021/ja308221z