The Phosin PptA Plays a Negative Role in the Regulation of Antibiotic Production in Streptomyces lividans

• Published in: Antibiotics (Basel) Vol. 10; no. 3; p. 325
• Main Authors: Shikura, Noriyasu, Darbon, Emmanuelle, Esnault, Catherine, Deniset-Besseau, Ariane, Xu, Delin, Lejeune, Clara, Jacquet, Eric, Nhiri, Naima, Sago, Laila, Cornu, David, Werten, Sebastiaan, Martel, Cécile, Virolle, Marie-Joelle
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-03-2021; MDPI
• Subjects: Actinorhodin; Adenosine diphosphate; antibiotic; Antibiotics; Binding; Biosynthesis; CHAD domain; Disruption; E coli; Enzymes; Gene deletion; Genes; Hydrolase; Hypotheses; Kinases; Life Sciences; Lipids; Microbiology and Parasitology; Modules; Mutants; Phenotypes; pho regulon; Phosphate; Phosphates; Polyphosphate kinase; Polyphosphates; Proteins; Streptomyces lividans; Stress; antibiotic; phosphate; CHAD domain; pho regulon; polyphosphates
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics10030325

In
, 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,
, encoding a polyphosphate kinase, whose disruption greatly enhanced the weak antibiotic production of
. In the condition of energetic stress, Ppk utilizes polyP as phosphate and energy donor, to generate ATP from ADP. In this paper, we established that
is co-transcribed with its two downstream genes,
, encoding a phosin called PptA possessing a CHAD domain constituting a polyphosphate binding module and
encoding a nudix hydrolase. The expression of the
operon was shown to be under the positive control of the two-component system PhoR/PhoP and thus mainly expressed in condition of phosphate limitation. However,
can also be transcribed alone from their own promoter. The deletion of
resulted into earlier and stronger actinorhodin production and lower lipid content than the disruption of
, whereas the deletion of
had no obvious phenotypical consequences. The disruption of
was shown to have a polar effect on the expression of
, suggesting that the phenotype of the
mutant might be linked, at least in part, to the weak expression of
in this strain. Interestingly, the expression of
and that of the genes of the
regulon involved in phosphate supply or saving were strongly up-regulated in
and
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.