2-Octulosonic acid biosynthesis

The 3-deoxy-D-ma/ino-2-octulosonic acid 8-phosphate synthase (KDO synthase or KdoS EC 4.1.2.16) is an enzyme involved in the biosynthesis of the eight-carbon sugar KDO [63], a constituent of the capsular polysaccharides (K-antigens) and outer membrane lipopolysaccharides (LPS, endotoxin) of Gram-negative bacteria [156], as well as of the cell wall of algae and a variety of plants [157], In vivo, the enzyme catalyzes the irreversible addition of 26 to D-arabinose 5-phosphate (Ara5P, 32) to form KDO 8-phosphate 33 [158]. The... 

Brozek, K.A., Hosaka, K., Robertson, A.D., Raetz, C.R.H. Biosynthesis of lipopolysaccharide in Escherichia coli cytoplasmic enzymes that attach 3-deoxy-D-manno-octulosonic acid to lipid A. J Biol Chem 264 (1989) 6956-6966. 

ABSTRACT This article describes recent developments in the chemistry of an important family of complex monosaccharides which have diverse structures and participate in a wide range of biological processes. For example 3-deoxy-D-/n nno-2-octulosonic acid (KDO) is a key component of the lipopolysaccharides (LPS) of Grammnegative bacteria, 3-deoxy-D-araftmo-2-heptulosonic acid (DAH) is a key intermediate in the biosynthesis of aromatic amino acids in bacteria and plants. A number of their syntheses that were achieved by homologation reactions of the natural carbohydrate units using enzymatic or chemical methods, as well as by total synthetic approaches are here included. Special emphasis is placed on new methodologies and their correlation with the biosynthetic pathway of the corresponding ulosonic acids. 

The biosynthesis of the core presumably begins with the transfer of a 3-deoxy-D-mflfino-octulosonic acid (KDO) group from CMP-KDO to lipid A. This reaction was demonstrated in a cell-free system from . coli Olll. A soluble enzyme catalyzed the transfer of KDO onto added lipid A. However, treatment of lipid A with 0.2 M sodium hydroxide, which presumably splits off O-acyl groups, dramatically increased the amount of KDO transferred this could mean that KDO is normally transferred to a precursor (of lipid A) that is not yet acylated, but it is equally possible that the effect merely reflects... 

One direction of research in the area of antibacterial drugs was connected with the synthesis of phosphonic analogues of carbohydrates, such as 3-deoxy-o-ma/JMO-2-octulosonic acid. This was due to the fact that these analogues potentially targeted the biosynthesis of this acid and hence disrupted the outer membrane of all Gram-negative bacteria without affecting mammalian cells. 

An incomplete lipid-A component has been purified from a mutant of S. typhi-murium, whose growth and synthesis of 3-deoxy-D-mannc>-2-octulosonic acid 8-phosphate are temperature sensitive. Pulse-chase experiments showed that the incomplete lipid-A component is an intermediate in the biosynthesis of the... 

The transfer of the pyruvate unit as phosphoenolpyruvate (PEP) to aldoses results in 4-hydroxy-2-oxocarboxylic acid structures and constitutes an important natural C-C bond forming reaction for the biosynthesis of ulosonic [36] and sialic acids [37,38]. Important compounds such as N-acetylneuraminic acid, 3-de-oxy-D-manno-octulosonic acid (KDO), and 3-deoxy-D-araZ mo-2-heptulosonic acid 7-phosphate (DAHP), the precursor of shikimic acid, are formed in this way. 

Belunis, C. J., and Raetz, C. R. H. (1992). Biosynthesis of endotoxins purification and catalytic properties of 3-deoxy-D-ma no-octulosonic acid transferase from Escherichia coli. J. Biol. Chem. 267, 9988-9997. 

---