Our next Journal club will be on the 28th of October 2014 at 8 pm on this paper here:
Regulation of the AbrA1/A2 Two-Component System in Streptomyces coelicolor and the Potential of Its Deletion Strain as a Heterologous Host for Antibiotic Production by Sergio Rico, Ana Yepes, Héctor Rodríguez, Jorge Santamaría, Sergio Antoraz, Eva M. Krause, Margarita Díaz, Ramón I. Santamaría, published on October 10, 2014 DOI:10.1371/journal.pone.0109844
Streptomyces is a genus of actinobacteria, a group of Gram-positive soil bacteria with an unusual life cycle, involving substrate mycelium, formation of aerial hyphae and spore formation. They are prolific producers of bioactive metabolites, such as clavulinic acid or FK-506 and thus are of great interest for industry. The onset for the production of these metabolites usually happens when nutrients are limited and come along with the developmental stages. The regulation of antibiotic production has been extensively studied mainly in S.coelicolor which is one of the model organisms and many genetic tools are available. For more details see this review here: http://mmbr.asm.org/content/77/1/112.short
Regulation of the AbrA1/A2 Two-Component System in Streptomyces coelicolor and the Potential of Its Deletion Strain as a Heterologous Host for Antibiotic Production
By Sergio Rico, Ana Yepes, Héctor Rodríguez, Jorge Santamaría, Sergio Antoraz, Eva M. Krause, Margarita Díaz, Ramón I. Santamaría
Published on October 10, 2014DOI: 10.1371/journal.pone.0109844
The Two-Component System (TCS) AbrA1/A2 from Streptomyces coelicolor M145 is a negative regulator of antibiotic production and morphological differentiation. In this work we show that it is able to auto-regulate its expression, exerting a positive induction of its own operon promoter, and that its activation is dependent on the presence of iron. The overexpression of the abrA2 response regulator (RR) gene in the mutant ΔabrA1/A2 results in a toxic phenotype. The reason is an excess of phosphorylated AbrA2, as shown by phosphoablative and phosphomimetic AbrA2 mutants. Therefore, non-cognate histidine kinases (HKs) or small phospho-donors may be responsible for AbrA2 phosphorylation in vivo. The results suggest that in the parent strain S. coelicolor M145 the correct amount of phosphorylated AbrA2 is adjusted through the phosphorylation-dephosphorylation activity rate of the HK AbrA1. Furthermore, the ABC transporter system, which is part of the four-gene operon comprising AbrA1/A2, is necessary to de-repress antibiotic production in the TCS null mutant. Finally, in order to test the possible biotechnological applications of the ΔabrA1/A2strain, we demonstrate that the production of the antitumoral antibiotic oviedomycin is duplicated in this strain as compared with the production obtained in the wild type, showing that this strain is a good host for heterologous antibiotic production. Thus, this genetically modified strain could be interesting for the biotechnology industry.
1. Is the paper well written?
2. Were the methods appropriate?
3. Do the results reflect the conclusion?
4. What else could be done?