Mannosamine biosynthesis

In nature, NANA arises through condensation of phosphoenolpyruvic acid with A-acetyl-D-mannosamine (NAM) catalysed by the biosynthetic enzyme NANA synthase. Owing to the labile nature of phosphoenolpyruvate, the use of this reaction in the synthesis of NANA has been limited to whole-cell systems where this substance can be generated biosynthetically in situ Most recently, the NANA synthase reaction forms the basis of fermentation processes for total biosynthesis of NANA. ... 

We propose that the first step in NDP-kasugamine biosynthesis is 2-epimeriza-tion of the postulated UDP-A -acetyl-D-glucosamine precursor, which is suggested by the similarity of the KasQ protein with known UDP-(Af-acetyl-)D-glucosamine 2-epimerases and catalyzes the conversion to UDP-N-acetyl-D-mannosamine. To... 

Mannosamine inhibits GPI anchor biosynthesis [81]. Mannosamine incorporates almost exclusively into the second mannose position of the GPI [82] and prevents further elongation of the chain, thus, acting as a chain terminator [83,84]. 

Figure 22 Biosynthesis of sialosides. Sialic acid aldolases catalyze the aldol condensation of W-substituted mannosamines with pyruvate to produce sialic acids. CMP-sialic acid synthetases produce CMP-sialic acid from CTP and sialic acid. Sialic acid is transferred to acceptor molecules by sialyltransferases.

Generally, syntheses of DAHP, KDO and Neu5Ac are based on chain extension of an appropriate sugar unit electrophiles by a C3 nucleophiles, according to the biosynthetic pathway, shown in Scheme 1. Thus, the reaction of D-erythrose 4-phosphate (13) acting as a C4 electrophile with phosphoenolpyruvate (14, C3 nucleophile) creates DAHP [6]. Mutual relationship to this pathway concerns the biosynthesis of KDO and Neu5Ac, which are produced on the reaction of phosphoenolpyruvate with D-arabinose 5-phosphate (C5 electrophile) or A-acetyl-D-mannosamine 6-phosphate (C6 electrophile), respectively [5,12]. 

Scheme (2). Biosynthesis of Neu5Ac from phosphoenolpyruvate and W-acetyl-o-mannosamine (ManNAc, 15)...

S ATP + N-acetyl-D-mannosamine (<5> highly specific for ATP and N-acetyl-D-mannosamine [3] <4> metabolic pathway between hexoses and siahc acids [2] <4> enzyme is involved in sialic acid metabolism [5] <4> involved in N-acetylneuraminic acid metabolism, key enzyme in N-acetylneuraminic acid biosynthesis [6,9-11]) (Reversibility [1-12]) [1-12]... 

Ralton JE, Milne KG, Guther ML et al. The mechanism of inhibition of glycosylphosphatidylinositol anchor biosynthesis in Trypanosoma brucei by mannosamine. J Biol Chem 1993 268 24183-24189. 

Hinderlich S, Berger M, Keppler OT et al. (2001) Biosynthesis of N-acetylneuraminic acid in cells lacking UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosamine kinase. Biol Chem 382 291-297. 

Incorporation studies with radioactive glucosamine, galactosamine and mannosamine confirmed the biosynthesis of sialoglycoproteins in avian tissues (Channon et al. 1972, Scott and Anastassiadis 1978). 

A-acetyl-mannosamine is an important precursor for the biosynthesis of the nine carbon sugar acid, iV-acetyl-D-neuraminic acid (see section 10.5 and Fig. 10.8A) that is frequently found as a monosaccharide in glycoproteins and glyco-lipids (see Chapter 9). 

Warren, L., and Felsenfeld, H., 1961b, N-Acetyl-mannosamine-6-phosphate and N-acetylneuraminic acid-9-phosphate as intermediates in sialic acid biosynthesis, Biochem. Biophys. Res. Commun. 5 185-190. 

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