## 1 Introduction  
Inorganic polyphosphate (polyP) is a linear anionic polymer containing from several to hundreds of orthophosphate residues linked by energy-rich phosphoanhydride bonds. PolyP participates in the regulation of many cellular events [1; 2]. In mammals, polyP is involved in signal transduction cascades [3; 4; 5; 6; 7; 8], serves as a phosphorus reserve for apatite formation in bone growth and development [9; 10; 11; 12], and plays a role in blood coagulation [13; 14] and inflammation [15; 16; 17]. In bacteria, polyP and its associated enzymes are involved in stress response and virulence, in addition to the function of phosphate and energy reserve [2; 18; 19; 20; 21]. Also, it is involved in cell motility, biofilm formation, and controls the level of the stringent response factor guanosine 5'-diphosphate 3'-diphosphate (ppGpp) [2; 22], although it has been shown that ppGpp is not essential for polyP synthesis in _Escherichia coli_[23]. The role of polyP in oxidative stress response is associated with its protein-protective chaperone function [24; 25], and the metal ion-complexing function [26]. In yeast, the polyP activity as a phosphate reserve is well studied [27], and the enzymes of polyP metabolism are well characterized [28; 29; 30]. However, the role of polyP in oxidative and toxic metal stresses in yeast remains notably less explored.  
Knockout mutants lacking the genes encoding polyP-metabolizing enzymes serve as models for studying the role of polyP. For bacteria, the commonly used models are the _ppk1_ or _ppk2_-null strains lacking polyphosphate kinases and having a significantly decreased polyP level [2; 31; 32]. They provide the possibility of direct studying of the effect of a decreased polyP level on bacterial cells, including stress response.  
In yeast, it is not trivial to limit polyP synthesis without non-intended disturbance in stress response due to the following. The synthesis of the major part of polyP pool is provided by the vacuolar transporter chaperone (VTC) complex of the vacuolar membrane [28; 33]. The reduced polyP accumulation was observed in mutants without _VTC4_[34] and _VTC5_[33], and in knockout strains lacking subunits of vacuolar V-ATPase [35]. All such mutants either lack some components of the VTC complex, being deficient in V-ATPase assembly and stability [36], or lack V-ATPase per se. The V-ATPase itself plays a key role in the response to oxidative and heavy metal stress [37; 38; 39], thus its dysfunction hides possible polyP functions in stress response.  
This is why we had to design strains with enhanced expression of polyP hydrolyzing enzymes. The _S. cerevisiae_ strain overproducing the Ppn1 polyphosphatase is known to have a decreased polyP level [40], and can serve as a model for studying the role of polyP in stress response in yeast.  
Given the role of polyP in metal ion resistance in microorganisms [41], we expected that the Ppn1 polyphosphatase overproducing strain (CRN/PPN1) would be more sensitive to manganese excess than the control strain (CRN). Instead, CRN/PPN1 had enhanced resistance to manganese. This is explained by the pre-adaptive state of CRN/PPN1 in the normal medium, revealed by the high-throughput transcriptome profiling. Furthermore, the pre-adaptive state was characterized by up-regulation of the oxidative stress response genes, which provided enhanced resistance to oxidative stress.