Brown Michael R W, Kornberg Arthur
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16085-7. doi: 10.1073/pnas.0406909101. Epub 2004 Nov 1.
Inorganic polyphosphate (poly P), in chains of tens to hundreds of phosphate residues, linked by high-energy bonds, is environmentally ubiquitous and abundant. In prebiotic evolution it could have provided a flexible, polyanionic scaffold to assemble macromolecules. It has been conserved in every cell in nature. In prokaryotes, a major poly P synthetic enzyme is poly P kinase 1 (PPK1), which is found in 100 bacterial genomes, including numerous pathogens. Null mutants of PPK1, with low poly P levels, are defective in survival: namely, they show defective responses to physical/chemical stresses and predation. Pathogens with a PPK1 deletion are defective in biofilm formation, quorum sensing, general stress and stringent responses, motility, and other virulence properties. With the exception of Dictyostelium, PPK1 is absent in eukaryotes and provides a novel target for chemotherapy that would affect both virulence and susceptibility to antibacterial compounds. Remarkably, another PPK in Dictyostelium discoideum (PPK2) is an actin-related protein (Arp) complex that is polymerized into an actin-like filament, concurrent with its reversible synthesis of a poly P chain from ATP.
无机多聚磷酸盐（多聚P）由数十至数百个磷酸残基链组成，通过高能键相连，在环境中普遍存在且含量丰富。在生命起源前的进化过程中，它可能为组装大分子提供了一个灵活的聚阴离子支架。它在自然界的每个细胞中都得以保留。在原核生物中，一种主要的多聚P合成酶是多聚P激酶1（PPK1），在100种细菌基因组中都能找到，包括许多病原体。PPK1基因敲除突变体的多聚P水平较低，在生存方面存在缺陷：也就是说，它们对物理/化学应激和捕食的反应存在缺陷。缺失PPK1的病原体在生物膜形成、群体感应、一般应激和严格反应、运动性以及其他毒力特性方面存在缺陷。除了盘基网柄菌外，真核生物中不存在PPK1，这为化疗提供了一个新靶点，化疗既能影响毒力，又能影响对抗菌化合物的敏感性。值得注意的是，盘基网柄菌中的另一种PPK（PPK2）是一种肌动蛋白相关蛋白（Arp）复合体，它能聚合成肌动蛋白样细丝，同时从ATP可逆地合成多聚P链。
