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Biosynthesis of Lipid A: Acylation of UDP-GlcNAc

Posted by Admin | 22 Feb

In the past ten years, the research on endotoxin mainly focused on the biosynthesis pathway of E. coli K-12 lipids.

 

In the process of cell surface biosynthesis, UDP-N-acetylglucosamine (UDP-GlcNAc) is an important intermediate and a common precursor of peptidoglycan and lipid A, which plays an important role in the synthesis of surface polysaccharides. In LPS core polysaccharides and О CleNAc plays a key role in antigen binding.

 

UDP-GlcN and β- Hydroxytetradecanoic acid-carrier proteinβ- The precursor molecules of lipid A synthesis, such as hydroxy myristoyl-acyl carrier protein, hydroxy myristoyl-ACP), generate lipid A through the following series of reactions:

 

1. The formation of UDP - monoacyl acetylglucosamine

UDP-GlcNAc is β- Hydroxytetradecanoic-apolipoprotein β Hydroxytetradecanoic acid acylation generates UDP-3-monoacyl-GleNAc. This reaction is catalyzed by acyltransferase. The lax A gene located at 4 minutes of chromosome encodes acyltransferase.

 

2. Production of UDP-2, 3-diacyl glucosamine and lipid X

UDP-monoacyl acetylglucosamine is deacetylated on the amino group under the catalysis of N-deacetylase encoded by the lpxC gene and then transferred to the amino group under the catalysis of the product encoded by lpxD gene β- Hydroxytetradecanoic acid, thus producing UDP - diacyl glucosamine (UDP - 2, 3 - diacyl - GlcN). The UDP of UDP-lipoacylglucose is removed by pyrophosphatase to produce 1-phospho-2,3-dilipoacylglucosamine, which is commonly known as lipid X (lipid x).

 

3. Formation of lipid Ⅳ a

UDP-2, 3-diacyl glucosamine, and lipid X pass through β- The 1,6 pyrophosphate bond is connected and condensed to form a lipid skeleton. At this time, there are 2 in each sugar group β- Hydroxytetradecanoic acid, reducing glucosamine, has a phosphate group at the C-1 position. This reaction is catalyzed by the protein encoded by the lpxB gene. Then, under the catalysis of specific kinase, the C-4 'position of non-reducing glucosamine is phosphorylated to produce 1,4' - diphosphate tetradecyl glucosamine disaccharide, namely lipid Ⅳ a (lipid Ⅳ a).

 

4. Production of lipid A

The transition from lipid Ⅳ a to lipid A requires the addition of KDO at the C-6 'position of non-reducing glucosamine, and then the addition of two saturated fatty acids and polar groups such as phosphate. The specific mechanism of this reaction is still unclear.

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