TY  - JOUR
A1  - Rico, Sergio
A1  - Yepes, Ana
A1  - Rodriguez, Hector
A1  - Santamaria, Jorge
A1  - Antoraz, Sergio
A1  - Krause, Eva M.
A1  - Diaz, Margarita
A1  - Santamaria, Ramon I.
T1  - 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
JF  - PLOS ONE
N2  - 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 DabrA1/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 DabrA1/A2 strain, 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.
KW  - signal-transduction systems
KW  - biosynthetic gene-cluster
KW  - escherichia coli
KW  - response regulator
KW  - oviedomycin
KW  - expression
KW  - organization
KW  - integration
KW  - bacteria
KW  - sequence
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115151
SN  - 1932-6203
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Rodriguez, Héctor
A1  - Rico, Sergio
A1  - Yepes, Ana
A1  - Franco-Echevarría, Elsa
A1  - Antoraz, Sergio
A1  - Santamaría, Ramón I.
A1  - Díaz, Margerita
T1  - The two kinases, AbrC1 and AbrC2, of the atypical two-component system AbrC are needed to regulate antibiotic production and differentiation in Streptomyces coelicolor
JF  - Frontiers in Microbiology
N2  - Two-component systems (TCSs) are the most important sensing mechanisms in bacteria. In Streptomyces, TCSs-mediated responses to environmental stimuli are involved in the regulation of antibiotic production. This study examines the individual role of two histidine kinases (HKs), AbrC1 and AbrC2, which form part of an atypical TCS in Streptomyces coelicolor. gRT-PCR analysis of the expression of both kinases demonstrated that both are expressed at similar levels in NB and NMMP media. Single deletion of abrC1 elicited a significant increase in antibiotic production, while deletion of abrC2 did not have any clear effect. The origin of this phenotype, probably related to the differential phosphorylation ability of the two kinases, was also explored indirectly, analyzing the toxic phenotypes associated with high levels of phosphorylated RR. The higher the AbrC3 regulator phosphorylation rate, the greater the cell toxicity. For the first time, the present work shows in Streptomyces the combined involvement of two different HKs in the response of a regulator to environmental signals. Regarding the possible applications of this research, the fact that an abrC1 deletion mutant overproduces three of the S. coelicolor antibiotics makes this strain an excellent candidate as a host for the heterologous production of secondary metabolites.
KW  - halstedii JM8
KW  - biosynthesis
KW  - expression mutants
KW  - domain genes A3(2)
KW  - two-component systems
KW  - Streptomyces
KW  - antibiotic production
KW  - histidine kinases
KW  - heterologous production
KW  - activation
KW  - response regulator
KW  - PCR
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143048
VL  - 6
IS  - 450
ER  -