2-Octulosonic acid phosphate

Deoxy-i>maw f)-2-octulosonic acid 8-phosphate can be obtained in gram quantities by using KDO synthase (F.C 4.1.2.16) for the addition of PEP to D-arabinose 5-phosphate33. DA HP synthase (EC 4.1.2.15) produces 3-deoxy-L>-arer/>/>io-heptulosonic acid 7-phosphate from PEP and D-erythrose 4-phosphate35. 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

Two of the most frequent monosaccharide components of bacterial polymers belonging to this group have been the subjects of articles in this Series. They are 3-deoxy-D-manno-2-octulosonic acid,247 a normal constituent of the core region of bacterial lipopolysaccharides that is also present in some other polymers, and N-acetylneuraminic acid,248 found in several capsular polysaccharides. Enolpyruvate phosphate serves as the precursor of the C-l-C-3 fragment of the monosaccharides, with D-arabinose 5-phosphate or 2-acetamido-2-deoxy-D-mannose 6-phosphate being an acceptor for transfer of the three-carbon unit. Characteristic, activated forms of these monosaccharides are the CMP derivatives. 

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... 

Abbreviations Abe, abequose Man, mannose Rha, rhamnose Gal, galactose Gic. glucose GlcN Ac, N-acetyl-glucosamine Hep, / lycero-/)-manno/joctulosonic acid Etn, ethanolamine FA. fatty acids-, Gy, phosphate. Mutants that produce incomplete polysaccharide are designated Ra to Re and are indicated by the solid lines SI. PS refers to wild type I. PS. Position and number of fa tty acids linked to lipid A have been updated by Westpha et al. (46). 

In the third pathway for the formation of 3-deoxyulosonic acids, enol pyruvate phosphate and an aldose phosphate are condensed, yielding orthophosphate and a 3-deoxyulosonic acid phosphate. In addition to formation of 3-deoxy-n-araInno-heptulosonic acid 7-phosphate, another example of this type of reaction is the formation of a 3-deoxyoctulosonic acid 8-phosphate (probably 3-deoxy-D-jfJMCo-octulosonic acid) from enolp3Tmvate phosphate and D-arabinose 5-phosphate. These reactions, unlike those involving pjrruvate, proceed completely to the right and have, so far, not been reversed. 

Obituary, of Emil Heuser, 1 Octulosonic acid, 3-deoxy-, 8-phosphate, 254... 

KD08P 3-deoxy-D-/nanno-2-octulosonate acid-8-phosphate... 

Other Aldolases. In addition to the DHAP aldolases, we have conducted preliminary investigations of two other aldolases. KDO synthase (E.C. 4.1.2.16) catalyzes the formation of 2-keto-3-deoxy-L-nrahi/io-octulosonic acid 8-phosphate (KDO-8-P) from arabinose 5-phosphate and PEP (Scheme 10) (29). KDO is an integral component of Gram-negative bacterial cell walls, and derivatives of KDO are of interest as inhibitors of cell wall formation (30, 31). 

Figure 2.9 Generalized structures of lipopolysaccharide and lipid A. Abbreviations Abe, abequose Man, Mannose Rha, rhamnose Gal, galactose Glc, glucose Hep, heptose KDO, 3-deoxy-D-manno-octulosonic acid 0, phosphate EtN, ethanolamine M, myristate Mo, y3-hydroxymyristate. Reproduced with permission from Harwood and Russell (1984).

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. 

Deoxv-D-manno-2-octulosonic acid (KDO) has been linked with the following sugars allyl KDO glycoside (4-linkage, a- and 6-anomers), D-glucosamine 4-phosphate(6-a-linkage), and... 

Deoxy-D-wfl/mo-octulosonic acid 8-(dihydrogen phosphate) has been synthesized by base-catalysed condensation of 2-O-benzyl-D-arabinose 5-phosphate with oxalacetate, followed by hydrogenolytic removal of the protecting benzyl group (Scheme 70). It is necessary to use the 2-0-benzyI derivative, since D-arabinose 5-phosphate undergoes spontaneous isomerization to n-erythro-pentulose 5-phosphate, The 9-O-acetyl and 4,9-di-O-acetyl derivatives of the... 

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