Page 204 - The Biochemistry of Inorganic Polyphosphates

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Applied aspects of polyphosphate biochemistry
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glucose 1-phosphate and UTP, and the isomerization of UDP-Glc to UDP-Gal, respectively.
The galactosyltransferase transfers galactose from UDP-Gal to N-acetylglucosamine,
yielding N-acetyllactosamine. The UDP formed through the galactosyl transfer reaction
should be regenerated to UTP under the action of PPK in the presence of PolyP. 14 mM
N-acetyllactosamine was accumulated after 48 h of reaction, even if only 4 mM UTP was
initially added, thus demonstrating that PPK and PolyP efficiently catalyse the regenera-
tion of UTP from UDP. It is obvious that PolyP and PPK can replace PEP and pyruvate
kinase in the regeneration of NTPs and are available for enzymatic cyclic synthesis of
oligosaccharides (Shiba et al., 2000).
When CMP-N-acetyl neuraminic acid synthetase (EC 2.7.7.43) of Haemophilus influen-
zae, polyphosphate kinase and CMP kinase were added to the reaction mixture contain-
ing equimolar concentrations (15 mM) of CMP and N-acetyl neuraminic acid, and PolyP
(150 mM in terms of phosphate), CMP-N-acetyl neuraminic acid was synthesized up to
67 % yield (Ishige et al., 2001).
It can be expected that the potential of PolyP as a phosphodonor in the enzymatic
synthesis of biologically active compounds will not be depleted.

9.3 Polyphosphates in Medicine

9.3.1 Antiseptic and Antiviral Agents

PolyPs display antiseptic, cytoprotective and antiviral activities. At a concentration of 0.1 %
or higher, PolyP had a bacteriocidal effect on log arithmic-phase Bacillus cereus cells (Maier
etal.,1999).ThegrowthinhibitioneffectofPolyPwasobservedwithStaphylococcusaureus
(Jen and Shelef, 1986; Matsuoka et al., 1995) and Aeromonas hydrophila (Palumbo et al.,
1995).
PolyP with a chain length of more than four P i residues inhibited human immunodefi-
ciency virus type 1 (HIV-1) infection of cells in vitro at concentrations of ≥ 300 µM (in
terms of P i residues), whereas PolyP 3 was ineffective (Lorenz et al., 1997b). This long-chain
PolyP also inhibited HIV-1-induced syncytium formation. The anti-HIV effect of PolyPs
may be due to the binding of the compounds to both the host cell surface and the virus,
thereby inhibiting adsorption of the virus (Lorenz et al., 1997b).

9.3.2 Polyphosphate Kinase as a Promising
Antimicrobial Target

The ppk1 and ppk2 sequences encoding prokaryotic polyphosphate kinases have a high
degree of conservation among diverse bacterial species, including some of pathogens of the
major infectious diseases (Tzeng and Kornberg, 1998; Zhang et al., 2002). In view of the
essentiality of polyphosphate kinase and PolyP for stationary phase responses and viability
in E. coli (Rao and Kornberg, 1996), Vibrio cholerae (Ogawa et al., 2000b), Pseudomonas
aeruginosa (Rashid et al., 2000a,b), Helicobacter pylori (Shirai et al., 2000), Shigella and
Salmonella (Kim et al., 2002) and Porphyromonas gingivalis (Chen et al., 2002), their