Ramón Santamaría

Streptomyces’ gene regulation

Our research is focused in three main aspects of Streptomyces biology:

  1. Streptomyces species produce a broad variety of antibiotics.
  2. They produce large amounts of hydrolytic enzymes with industrial potential
  3. Streptomyces is a normal inhabitant of soil where they interact with other organisms.

In recent years we have studied the putative involvement of several S. coelicolor two components systems in the regulation of antibiotic production (Yepes et al. 2011). Our current research is focused in two of them that affect positively or negatively antibiotic production. One of these systems is an atypical system having two histidine kinases and a regulator that is phosphorylated by both kinases (Rico et al. under review). Our objective is to have a detailed information about the regulation exerted by these systems in order to get strains able to express and overproduce comercial antibiotics in high amounts.

Other of our interest is to develop expression vectors for Streptomyces. Based in our previous work related with hydrolytic enzymes we have selected several strong promoters regulated by the carbon source present in the culture media that permit the overexpression of different proteins of industrial interest (Diaz et al. 2008, Aragon et al. 2013). Besides the search for strong regulated promoters, we are interested in the development of vectors with positive selection that do not require the addition of antibiotic for maintenance. Up to now we have covered this objective using a Streptomyces toxin antitoxin system that we have described recently in and their use is very promising (Sevillano et al. 2012, 2013).

Due that the Streptomyces are common soil microorganisms they may interact positive or negatively with other organisms of the habitat to improve their survival. Therefore, other subject of our work is to validate the hypothesis that these interespecific interactions might be the responsible of triggering in their natural endeavour of many of pathways present in Streptomyces genome and that are silenced in laboratory conditions. The study that we have performed, shows that the stimulation of antibiotic production really occurs in cocultures of  Streptomyces and Myxococcus (Perez et al. 2011).

Group members
Ramón Santamaría Scientist (CSIC)
Margarita Díaz Associate Professor (USAL)
Laura Sevillano Postdoctoral
Sergio Antoraz PhD Student
María Tejada PhD Student
Rachael Hattam Erasmus Student
Ana Martínez-Carrasco Pérez Technician
Recent publications
Rodríguez H, Rico S, Yepes A, Franco-Echevarria E, Antoraz S, Santamaría RI and Díaz M (2015).
The two kinases, AbrC1 and AbrC2, of the atypical two-componentsystem AbrC are needed to regulate antibiotic production and differentiation in Streptomyces coelicolor
Frontiers in Microbiology 6:450.
Antoraz S, Santamaría RI, Díaz M, Sanz D and Rodríguez H (2015).
Toward a new focus in antibiotic and drug discovery from the Streptomyces Arsenal
Frontiers in Microbiology 6:461 .
Rico S, Yepes A, Rodríguez H, Santamaría J, Antoraz S, Krause E, Díaz M and Santamaría RI (2014)
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
PLoS One 9:e109844.
Rico S, Santamaría RI, Yepes A, Rodríguez H, Laing E, Bucca G, Smith CP and Díaz M. (2014)
Deciphering the regulon of the Streptomyces coelicolor AbrC3, a positive response regulator of antibiotic production.
Appl. Environ. Microbiology 80: 2417-2428
Rodríguez H, Rico S, Díaz M and Santamaría RI (2013)
Two-component systems in Streptomyces: key regulators of antibiotic complex pathways
Microbial Cell Factories 12:127
Research grants
MINECO:PCIN-2014-067
MINECO: BFU2010-17551
Junta Castilla y León: CSI099A12-1
Links of interest