## 1 Introduction  
The Phosin PptA Plays a Negative Role in the Regulation of Antibiotic Production in _Streptomyces Ividans_[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [5  
## 1 Introduction  
_Streptomyces_ are Gram-positive, filamentous soil bacteria, of great medical and economic importance since they are able to produce a great variety of bio-active molecules useful to human health or agriculture [1; 2]. The biosynthesis of these molecules usually takes place when growth slows down or stops and is thought to be triggered by some nutritional limitation [3]. One of the most efficient triggers of antibiotic production is a limitation in phosphate that is correlated with a low ATP content (weak energetic state) [4; 5]. Conversely, antibiotic production is strongly repressed in condition of high phosphate availability. Inorganic phosphate being often a limiting nutrient in the environment, living systems have developed ways to store it efficiently as polyphosphates, in stressful conditions [6; 7]. Polyphosphates (polyP) are linear polymers of phosphate linked by highly energetic phosphoanhydride bonds. Their synthesis relies, at least in part, on the action of polyphosphate kinases, enzymes able to polymerize the \(\gamma\) phosphate of ATP into polyphosphate [8]. However, since some polyP were still present in the _ppk_ mutant of _E. coli_[9], alternative mechanisms of polyP synthesis are likely to exist. The accumulation of large quantities of polyP was noticed in _phoU_ mutants of _E. coli_[10] and was correlated with an activation of Pi up-take by the PstSCAB transport system. This suggested that active Pi up-take contributes to polyP synthesis. Polyphosphates are involved in the resistance to various stresses [11; 12; 13] and constitute an important intracellular reserve of phosphate and energy that can be mobilized in condition of phosphate and energetic stress [14]. In such conditions, polyphosphates can either be used as a phosphate and energy donor to generate ATP from ADP by enzymes possessing adenosine diphosphate kinase-like activities, such as Ppk (SCO4145/SLI_4383) in _Streptomyces_[15; 16] or as a an inorganic phosphate supplier via its degradation by endo and/or exo-polyphosphate phosphatases. In _Streptomyces_ species, antibiotic biosynthesis being triggered in condition of phosphate limitation, getting a better understanding of the role played by this important polymer in the regulation of antibiotic biosynthesis is of crucial importance. We previously characterized the polyphosphate kinase (Ppk) encoding gene of _S. lvidans_ (_SLI_4384_) and demonstrated that, _in vitro_, Ppk can act either as a polyphosphate kinase, synthetizing polyphosphate from ATP, or as an adenosine diphosphate kinase, regenerating ATP from ADP and polyP, depending on the ATP/ADP ratio in the reaction mix [15]. In _S. lvidans_, _ppk_ is mainly expressed in Pi limitation and belongs to the Pho regulon [16; 17]. _In vivo_, in Pi limitation, the polyP and ADP content of the _ppk_ mutant was shown to be higher than that of the _wt_ strain, suggesting the absence of a polyP-dependent regeneration process of ADP into ATP [5]. However, unexpectedly the ATP content of the strain was similar to that of _the wt_ strain, suggesting that homeostatic processes, similar to those occurring in _S. colicolor_, are being triggered in this strain in order to re-establish its energetic balance [5]. Consistently, in Pi limitation, the deletion of _ppk_ led to a huge increase of the weak antibiotic production of _S. lividans_ that was correlated with a lower total lipid content, as in _S. colicolor_[5; 15]. Interestingly, the proteins encoded by the two genes located immediately downstream of _ppk_ have similarities with proteins possibly involved in polyP metabolism.