Streptomyces' gene regulation

Our research is based on two main premises related to the biology of Streptomyces:

  1. They produce a wide variety of bioactive molecules against bacteria, fungi, etc., and have, in their genome, a very large number of silenced biosynthetic pathways that are not expressed under laboratory conditions.
  2. They are ubiquitous, live in complex ecosystems and are a group with a huge number of species, many of them yet to be discovered.

The main objective of the group is to contribute unravel part of the complex regulation network of antibiotic production, isolate new producers and seek their biotechnological applications in improving their production by manipulating this regulation or using these microorganisms as biological control of plant pathogens.

To achieve this objective, we approach the research from three strategies:

  1. The study of different general regulators of antibiotic production such as two-component systems (TCSs), and XRE/DUF397 systems. The result of our work, in the TCSs, has been the description of several systems that regulate either positively, AbrC and Aor1, or negatively, AbrA and AbrB, the global production of antibiotics, as well as, in some cases, cell differentiation. Regarding the XRE/DUF397 systems, they are composed of a protein of the “Xenobiotic Response Elements” (XRE) type and a small protein with a DUF397 domain. We have shown that these systems, proposed bioinformatically by other authors as toxin/antitoxin systems, do not behave as such and their study has allowed us to describe a strong positive regulator of Scr1/Scr2 antibiotic production. Our objective is to know in detail the regulatory mechanisms exerted by both types of regulatory systems (TCSs or XRE/DUF397) in order to delete or overexpress them, depending on their regulatory role in the cell, and thus to get strains that will allow us in the future the expression and overproduction of antibiotics of commercial interest.
  2. Bacteria of the genus Streptomyces are common soil microorganisms where they interact positively or negatively with other organisms in the habitat. These interspecific interactions could be responsible for the activation, in their natural habitat, of many of the biosynthetic pathways present in the Streptomycesgenomes that are silenced under laboratory conditions. We are addressing this aspect performing co-cultures of Streptomyces with other microorganisms and analyzing the synthesized compounds by both partners in these conditions. At the same time, we are studying the effect of elicitors on the production of antibiotics.
  3. Since actinomycetes are the major producers of antimicrobial compounds and are ubiquitous, another strategy is to increase the potential arsenal of bioactive molecules produced by new actinomycetes. In this sense, we have already isolated a huge number of actinomycetes from diverse habitats such as alkaline soils, intestine and feces of xylophagous insects, wasp nests, etc. Thus, we have selected several microorganisms, mainly Streptomyces, which present a high potential against phytopathogenic fungi. This gives an applied value to our research on its use in biological control.
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 Scientific Researcher (CSIC)
Margarita Díaz Full Professor (USAL)
Carolina Riascos PhD Student
Javier García Martín PhD Student
María Lorenzo Sánchez PhD Student
Ramiro Morán Cacho Master Student
Eva López Delgado Laboratory Technician


Ramón Santamaría
Laboratory 1.9
Margarita Díaz
Laboratory 1.9

Publications, last 5 years

Sánchez De La Nieta, R., Santamaría, R.I.*, and Díaz, M.* (*:co-corresponding authors). (2022)
Two-Component Systems of Streptomyces coelicolor: An Intricate Network to Be Unraveled.
International Journal of Molecular Sciences International Journal of Molecular Sciences
Doi: 10.3390/ijms232315085
Santamaría, R.I*., Martínez-Carrasco., Martín, J., Tormo, J R., Pérez-Victoria, I., González, I., Genilloud, O., Reyes, F, and Díaz, M*. (*:co-corresponding authors) (2022)
Grapevine Xylem Sap Is a Potent Elicitor of Antibiotic Production in Streptomyces spp
Antibiotics 11(5):672
Doi: 10.3390/antibiotics11050672
Santamaría, RI.*, Martínez-Carrasco A., Sánchez de la Nieta R., Torres-Vila LM., Bonal R., Martín J., Tormo R., Reyes F., Genilloud O. and Díaz, M*. (*:co-corresponding authors) (2020)
Characterization of Actinomycetes Strains Isolated from the Intestinal Tract and Feces of the Larvae of the Longhorn Beetle Cerambyx welensii.
Microorganisms 8(12):2013
Doi: 10.3390/microorganisms8122013
Sánchez De La Nieta, R., Antoraz, S., Alzate, J.F., Santamaría, R. I.*, Díaz, M.* (*:co-corresponding authors). (2020)
Antibiotic production and antibiotic resistance: the two sides of AbrB1/B2, a two component system of Streptomyces coelicolor.
Frontiers in Microbiology 11:587750
Doi: 11:587750
Santamaría R.I.*, Sevillano, L., Martín, J., Genilloud, O., González, I., and Díaz, M* (*co-corresponding authors). (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
Romero-Fernández M., Moreno-Pérez S., Orrego A. H., Martins de Oliveira S., Santamaría R.I., Díaz M., Guisán JM., Rocha-Martín J. (2018)
Designing continuous flow reaction of xylan hydrolysis for xylooligosaccharides production in packed-bed reactors using xylanase immobilized on methacrylic polymer-based supports.
Bioresource Technology 266: 249-258
Doi: 10.1016/j.biortech.2018.06.070
Becerril, A., Álvarez, S., Braña, AF., Rico, S., Díaz, M., Santamaría, R.I., Salas, JA and Méndez, C. (2018)
Uncovering production of specialized metabolites by Streptomyces argillaceus: activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches.
PLOS ONE 13(5): e0198145
Doi: 10.3389/fmicb.2018.02791
Romero-Fernández M., Moreno-Pérez S., Martins de Oliveira S., Santamaría R.I., Guisán JM., Rocha-Martín J. (2018)
Preparation of a robust immobilized biocatalyst of β-1,4-endoxylanase by surface coating with polymers for production of xylooligosaccharides from different xylan sources.
New Biotechnology 44:50-58
Doi: 10.1016/j.nbt.2018.04.007

Research grants

MICINN: PID2019-107716RB-I00
MINECO: BIO2015-66958-R
Junta CyL: SA036G19