Synthesis lipid intermediates

A unique, membrane-associated, sialyltransferase system in E. coli has been described that catalyzes the synthesis of sialic acid polymers with the aid of sialyl-monophosphonoundecaprenol.293 In mammalian systems, no evidence was obtained lor the involvement of lipid intermediates in sialic acid transfer, or in the fonnation of sialyl-(2— -8) link-... 

The mechanism of synthesis of polysaccharides is a controversial issue. After discovery, by Cardini s group, that starch may be polymerized on a protein,152,153 it was suggested153 that all nascent, polysaccharide chains might be covalently associated with a protein. Connected with the formation of glycoprotein is the involvement of lipid intermediates. We shall analyze the biosynthetic pathways of polysaccharides where partial or complete evidence of this kind of mechanism has been educed. 

Little is known about the regulation mechanisms of the synthesis of complex carbohydrate in plants, through lipid intermediates. However, partial evidence indicates that lipid-mediated glycosylation in proteins could be a regulatory step. When glycosylation of carboxypeptidase Y is inhibited... 

Finally, details of the synthesis of heteropolysaccharides in plants are as yet completely unknown. The structural similarities among some plant gums and such bacterial exopolysaccharides as xanthan gum suggest that similar mechanisms may be operative in bacteria and in plants. Lipid intermediates could be suggested as potential glycosyl donors in the formation of plant gums and mucilages. 

In recognition of the difficulty in obtaining the lipid intermediates in quantities to facilitate detailed mechanistic study of the peptidoglycan biosynthetic enzymes, we initiated an effort directed toward a chemical synthesis of both lipid I and lipid II. As was the case with the fermentation/isolation protocols, we anticipated several technical challenges that would need to be addressed in order to reach the target compounds. These challenges, and their solutions, will be discussed in the sections that follow. 

The liposidomycins are a family of novel lipid-containing nucleoside antibiotics that were found in the culture filtrate and mycelia of Streptomyces griseoporeus These antibiotics, which have unique biological activity and structures, inhibit the formation of the lipid intermediate in bacterial peptidoglycan synthesis three times more than does tunicamycin and have extremely high specificity. The structures of liposidomycins B (1) and C were proposed on the basis of degradation and spectroscopic studies. They are identical except for slight variations in the lipid portion. 

All aspects relating to the bacterial cell wall structure have been reviewed recently. Among the topics covered are the cytoplasmic steps of peptidoglycan synthesis, Lipid II as biosynthetic intermediate and antibacterial target, PBP structure and catalysis, peptidoglycan hydrolytic remodeling, structural... 

S Additional information <1, 4> (<1> product of the reaction is a substrate for the synthesis of lipid intermediates in peptidoglycan synthesis [1] <1> the product of the reaction, Css-isoprenoid alcohol monophosphate functions in the biosynthesis of bacterial peptidoglycan and lipopolysac-charides [3] <4>, the enzyme predominantly affects growth of the cells under stress conditions [12]) [1, 3, 12]... 

Two unexpected findings in this system led Strominger and coworkers to the discovery of the lipid intermediates and of the complex sequence of reactions involved in the synthesis of linear peptidoglycan. One was the observation that UMP and inorganic... 

The synthesis of this polymer in a cell-free system has been achieved, and it was found that UDP-2-acetamido-2-deoxy-D-glu-copyranose donates the entire 2-acetamido-2-deoxy-D-glucopyranosyl phosphate moiety intact, and that CDP-D-glycerol donates the glycerol phosphate moiety. The presence of lipid intermediates in this system has been reported. ... 

Higashi Y, Strominger JL, Sweeley CC. Biosynthesis of the peptidoglycan of bacterial cell walls. XXI. Isolation of free Css-isoprenoid alcohol and of lipid intermediates in peptidoglycan synthesis from Staphylococcus aureus. J Biol Chem 1970 245-3697. 

Glaser, L. Lindsay, B. (1974) The Synthesis of Lipoteichoic Acid Carrier , Biochemical and Biophysical Research Communications, 59, 1131-6 Gold, M.H. Hahn, H.J. (1976) Role of a Mannosyl Lipid Intermediate in the Synthesis of Neurospora crassa Glycoproteins, Biochemistry, 15,1808-14 Goldemberg, S.H. Marechal, L.R. (1963) Biosynthesis of Paramylon in Euglena gracilis, Biochimica et Biophysica Acta, 71, 743-4... 

The synthesis of SG (and ASG) by cell-free particulate fractions from plants has been reported by many researchers (e.g., Hou et al., 1%7, 1%8 Eichenberger and Newman, 1%8 Kauss, 1968 Ongun and Mudd, 1970 La-vintman and Cardini, 1970). In many cases the research interest was in polysaccharide biosynthesis and the possible involvement of lipid intermediates. There is no evidence that glycosylated sterols participate in the synthesis of polysaccharides. 

---