Alpha-Methylthiolincosaminide (MTL) is the octose moiety of the clinically important lincomycin antibiotics. Previous studies have demonstrated that MTL (C8 unit) is biosynthetically derived from condensation of a C5 unit such as ribose-5-phosphate with a C3 donor molecule such as sedoheptulose-7-phosphate probably by a transaldolase reaction. The proposed investigation will examine in detail the biosynthetic steps between condensation of the C5 unit and C3 unit and the formation of MTL by Streptomyces lincolnensis. Using primarily 13C-NMR we propose to identify both the C5 unit and the C3 donor molecule which condense to form the purported octulose-8-phosphate and in turn its conversion to octose-8-phosphate. A retrospective biosynthetic analysis leads us to suspect that the 8-deoxyoctose may be formed by an analogous reaction to the TDP-D-glucose oxidoreductase reaction. We will examine this possibility and determine the stereochemical course of the reaction by analysis of the chiral C-8 methyl group produced in MTL. Lastly we propose to examine the origin of the S-CH3 found in MTL.
