The Phosin PptA Plays a Negative Role in the Regulation of Antibiotic Production in _Streptomyces Ividans_  
[PERSON]  
1 Institute for Integrative Biology of the Cell (2 BC), Universite Paris-Saclay, CEA, CNRS, 91196 Gif-sur-Yvette, France; [EMAIL_ADDRESS] (N.S.); [PERSON]@2 bc-paris-saclay.fr (E.D.); [EMAIL_ADDRESS] (C.E.); [EMAIL_ADDRESS] (D.X.); [PERSON]S] (C.L.); [PERSON]@2 bc-paris-saclay.fr (L.S.); [PERSON]@12 bc-paris-saclay.fr (D.C.); [PERSON]@2 bc.paris-saclay.fr (C.M.)
2 Laboratoire de Chimie Physique (LCP), CNRS UMR 8000, Universite Paris-Saclay, 91405 Orsay, France; [PERSON]]
3 Department of Ecology, Institute of Hydobiology, School of Life Science and Technology, Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, Engineering Research Center of Tropical and Subtropical Aquatic Ecological Engineering, Ministry of Education, Jinan University, Guangzhou 510632, China
4 Institut de Chimie des Substances Naturelles, CNRS, Universite Paris Saclay, 91190 Gif-sur-Yvette, France; [PERSON]SS] (E.J.); [PERSON]RESS] (N.N.)
5 Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria; [PERSON]###### Abstract  
In _Streptomyces_, antibiotic biosynthesis is triggered in phosphate limitation that is usually correlated with energetic stress. Polyphosphates constitute an important reservoir of phosphate and energy and a better understanding of their role in the regulation of antibiotic biosynthesis is of crucial importance. We previously characterized a gene, _SLL_4384/_ppk_, encoding a polyphosphate kinase, whose disruption greatly enhanced the weak antibiotic production of _Streptomyces Ividans_. In the condition of energetic stress, Ppk utilizes polypA as phosphate and energy donor, to generate ATP from ADP. In this paper, we established that _ppk_ is co-transcribed with its two downstream genes, _SLL_4383_, encoding a phosin called PptA possessing a CHAD domain constituting a polyphosphate binding module and _SLL_4382 encoding a nudix hydrolase. The expression of the _ppk/pptA/SLL_4382_ operon was shown to be under the positive control of the two-component system Prob/RhoP and thus mainly expressed in condition of phosphate limitation. However, _pptA and _SLL_4382_ can also be transcribed alone from their own promoter. The deletion of _pptA_ resulted into earlier and stronger actinorhodin production and lower lipid content than the disruption of _ppk_, whereas the deletion of _SLL_4382_ had no obvious phenotypical consequences. The disruption of _ppk_ was shown to have a polar effect on the expression of _pptA_, suggesting that the phenotype of the _ppk_ mutant might be linked, at least in part, to the weak expression of _pptA_ in this strain. Interestingly, the expression of _ploR/photoP_ and that of the genes of the _pho_ regulon involved in phosphate supply or saving were strongly up-regulated in _pptA_ and _ppk_ mutants, revealing that both mutants suffer from phosphate stress. Considering the presence of a polyphosphate binding module in PptA, but absence of similarities between PptA and known exo-polyphosphatases, we proposed that PptA constitutes an accessory factor for exopolyphosphatases or general phosphatases involved in the degradation of polyphosphates into phosphate.  
phosphate; polyphosphates; CHAD domain; antibiotic; pho regulon 2021