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 one of the goals of our research group has been to deep inside the complex regulatory network of antibiotic production and look for biotechnological applications in the improvement of this production by manipulating this regulation. We study the connexion between the upper part of the cascade regulation (the signal that triggers it) and the final product (antibiotics). In fact, we are focused in the study of two-component systems (TCSs), the principal signal transduction mechanism in bacteria, that mediates as a response the production of antibiotic. We have already described several TCSs implied in a global antibiotic regulation either positively, AbrC and Aor1, or negatively, AbrA and AbrB (unpublished results) and in some cases they are also implied in cellular differentiation. This work has been done in Streptomyces coelicolor, in which genome ( are more than 100 TCSs, being at least 15 of them related to antibiotic production. We pretend to add more elements to the regulatory network and to apply the previous results in biotechnological processes. The objective is to understand the mechanism of action of these TCSs to delete them or overexpress them, depending on their role in the cell, and by this way to get strains for future expression and over production of antibiotics with industrial interest.

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. 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.

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 with other microorganisms.

Colonies of  Streptomyces coelicolor; Protein production in Streptomyces lividans; Mycelium of S. coelicolor grown in liquid medium; Schematic representation of the Aor1 regulation; Cloning of heterologous routes and antibiotic production

Figures. Colonies of Streptomyces coelicolor ; Protein production in Streptomyces lividans ; Mycelium of S. coelicolor grown in liquid medium; Schematic representation of the Aor1 regulation; Cloning of heterologous routes and antibiotic production

Image description

Group members

Ramón Santamaría Scientist (CSIC)
Margarita Díaz Associate Professor (USAL)
Ricardo Sánchez de la Nieta PhD Student
Carolina Riascos PhD Student
Laura García Master Student
María Marugán Grade Student
Rosa Álvarez Palencia JAE Intro Student CSIC
Ana Martínez Carrasco Technician


Ramón Santamaría
Laboratory 1.9
Margarita Díaz
Laboratory 1.9

Recent publications

Santamaría R.I., Sevillano, L., Martín, J., Genilloud, O., González, I., and Díaz, M. (2018)
The XRE-DUF397 protein pair, Scr1 and Scr2, acts as a strong positive regulator of antibiotic production in Streptomyces.
Frontiers in Microbiology 9:2791
Doi: 10.3389/fmicb.2018.02791
Sevillano L, Díaz, M*, and Santamaría, RI*. (*co-corresponding authors) (2017)
Development of an antibiotic marker‑free platform for heterologous protein production in Streptomyces.
Microbial Cell Factories 16:164
Antoraz S, Rico S, Rodríguez H, Sevillano L, Alzate JF, Santamaría RI* and Díaz M* (*co-corresponding authors) (2017)
The orphan response regulator Aor1 is a new relevant piece in the complex puzzle of Streptomyces coelicolor antibiotic regulatory network.
Frontiers in Microbiology 8:2444
Doi: 10.3389/fmicb.2017.02444
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
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

Research grants

MINECO: BIO2015-66958-R
MINECO: PCIN-2014-067
Junta CyL: SA036G19