Vancosamine Biosynth Part 1 on:
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Vancosamines are aminosugars that are a part of
EvaC then methylates molecule 3 at the 3-C to form molecule 4 by deprotonating to form an enolate intermediate, which then attacks a SAM methyl group in the active site of EvaC. EvaD then epimerizes molecule 4 at 5-C to form molecule 5. Finally, EvaE can form either epi/vancosamine by reduction using either 
The vancosamines are then used by the cell to synthesized vancomycin and related molecules. A glycosyltransferase attaches the amino sugar through α-1 ether linkages.
Additional modifications are possible at the 3-C amino group to create ''N''-alkyl or ''N''-acyl derivatives of this sugar.
vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...
and other molecules within the vancomycin family of antibiotics. Vancosamine synthesis is encoded by the vancomycin (''vps'') biosynthetic cluster. Epivancosamine, a closely related aminosugar, is encoded by the chloroeremomycin (''cep'') biosynthetic cluster.
History
Vancosamine was first isolated by Lomakina ''et al'' in 1968. In 1972, Johnson ''et al'' were the first to identify and completely characterize vancosamine. Epivancosamine was subsequently isolated in 1988 by Hunt ''et al'' atEli Lilly
Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
Biosynthesis
The biosynthesis of vancosamine and epivancosamine are identical, except in the last step. The enzymes that catalyze the reactions have been designated EvaA-E. A molecule of TDP-D-glucose enters the pathway via conversion to molecule 1 by an oxidoreductase enzyme and then a dehydratase enzyme. In the next step, EvaA dehydrates molecule 1 by deprotonating at 3-C to form and enolate, which then eliminates 2-OH, to form molecule 2. Molecule 2 is transformed into molecule 3 by tautomerizing to its keto form and then being transaminated by EvaB using L-Glu as the ammonia source and PLP as a cofactor. :
EvaC then methylates molecule 3 at the 3-C to form molecule 4 by deprotonating to form an enolate intermediate, which then attacks a SAM methyl group in the active site of EvaC. EvaD then epimerizes molecule 4 at 5-C to form molecule 5. Finally, EvaE can form either epi/vancosamine by reduction using either NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
or NADPH
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
to reduce the carbonyl at 4-C. The stereochemical outcome is dependent on the EvaE that is encoded in the biosynthetic cluster. Vancomycin ''vps'' EvaE results in vancosamine, whereas chloroeremomycin ''cep'' EvaE results in epivancosamine.
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The vancosamines are then used by the cell to synthesized vancomycin and related molecules. A glycosyltransferase attaches the amino sugar through α-1 ether linkages.
Additional modifications are possible at the 3-C amino group to create ''N''-alkyl or ''N''-acyl derivatives of this sugar.
Total syntheses
Several syntheses of vancosamine have been published.Parker, K. A., Chang, W. "A Synthesis of L-Vancosamine Derivatives from Non-Carbohydrate Precursors by a Short Sequence Based on the Marshall, McDonald, and Du Bois Reactions." ''Org. Lett.'' 2003, ''5'' (21), 3891-3893.See also
*Vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...
* Oritavancin
Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vanc ...
* Glycopeptide antibiotic
Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective antibiotics vancomycin, teicoplanin, ...
s
References
{{reflist Amino sugars