Mª Carmen Méndez Fernández
Carlos Olano Álvarez

Departamento de Biología Funcional. Area de Microbiología.
Facultad de Medicina.
C/ Julian Clavería s/n
33006, Oviedo


Biosynthesis of Antitumor Molecules group (BMA) research lines of have as main objective the generation of novel derivatives of antitumor compounds.

Lab web page

Several techniques of genetic engineering are applied for this purpose to microorganism in order to identify, isolate and characterize gene clusters involved in the biosynthesis of antitumor compounds and their manipulation. This manipulation consist, in general terms, in genetic inactivation and the ectopic expression of genes from two or more biosynthesis gene clusters in the producer microorganism of an specific antitumor compound. The objective of those approaches, named Combinatorial Biosynthesis”, is the generation of novel molecules with structural characteristics different from the original natural product, thus generating hybrid molecules.

In the present we are also focusing our attention in the identification and isolation of novel antitumor compounds produced by actinomycetes isolated from leaf-cutting ants from Peru. In this research line we are sequencing genomes of these actinomycetes in order to identify silent clusters, in standard culture laboratory conditions, which will be then activated using genetic engineering. The selection of these silent clusters will be based in the analysis of the novelty of the deduced structural characteristics of each compound determined by bioinformatics analysis.

Furthermore, we are also interested on the study of metabolic pathways and regulatory mechanisms involved in the biosynthesis of antitumor compounds in order to improve the production of the novel antitumor derivatives generated.

Research lines:

• Characterization of antitumor compounds biosynthesis pathways.
• Generation of novel antitumor compounds by combinatorial biosynthesis.
• Production improvement of antitumor compounds.
• Metabolic engineering of biosynthesis pathways.
• Genome mining to activate silent pathways for the discovery of novel antitumor compounds.


Carmen Méndez graduated from the University of Oviedo, Spain, in 1984 with a Ph.D. based on the characterization of events that take place during the differentiation processes of colonies of Streptomyces antibioticus. After a post-doctoral stay in Keith Chater’s laboratory in Norwich, UK, she returned to Oviedo, Spain, where she became Associate Professor in Microbiology in 1988. Since 2011 she has been a Full Professor of Microbiology at the University of Oviedo. Her major interests are the cloning and characterization of biosynthetic pathways of antibiotics and antitumor compounds in actinomycetes, the generation of novel compounds with potential antibiotic or antitumor activities through combinatorial biosynthesis, and the activation of silent pathways in actinomycetes.

Carlos Olano graduate in Biology (1991), PhD in Biology and Extraordinary PhD Thesis Award (1995) by the University of Oviedo (Spain). After a postdoctoral period at the School of Pharmacy, University of Wisconsin (Madison, WI, USA), reincorporates at the University of Oviedo as research assistant of the University Institute of Oncology from Principado de Asturias (IUOPA). Later he got a position as Associate Professor at the University of Oviedo and Professor at 2021. He forms part, from the beginning, of the University of Oviedo research team “Biosynthesis of bioactive compounds by microorganisms (BIOMIC)”. C. Olano present research interests are: identification of novel secondary metabolism pathways using genome mining; identification of novel bioactive compounds; isolation and characterization of novel biosynthesis gene clusters  (BGC)  leading to novel bioactive compounds; use of combinatorial biosynthesis to generate novel derivatives; and the activation of cryptic/silent BGCs using genetic engineering approaches.


  • Prado-Alonso L, Pérez-Victoria I, Malmierca MG, Montero I, Rioja-Blanco E, Martín J, Reyes F, Méndez C, Salas JA, Olano C. (2022).  Colibrimycins, Novel Halogenated Hybrid Polyketide Synthase-Nonribosomal Peptide Synthetase (PKS-NRPS) Compounds Produced by Streptomyces sp. Strain CS147. Appl Environ Microbiol. 88(1): e0183921.
  • Ceniceros A, Cuervo L, Méndez C, Salas JA, Olano C, Malmierca MG. (2021).  A Multidisciplinary Approach to Unraveling the Natural Product Biosynthetic Potential of a Streptomyces Strain Collection Isolated from Leaf-Cutting Ants. Microorganisms. 9(11): 2225.
  • Botas A, Eitel M, Schwarz PN, Buchmann A, Costales P, Núñez LE, Cortés J, Morís F, Krawiec M, Wolański M, Gust B, Rodriguez M, Fischer WN, Jandeleit B, Zakrzewska-Czerwińska J, Wohlleben W, Stegmann E, Koch P, Méndez C, Gross H. (2021). Genetic Engineering in Combination with Semi-Synthesis Leads to a New Route for Gram-Scale Production of the Immunosuppressive Natural Product Brasilicardin A. Angew Chem Int Ed Engl. 60(24): 13536-13541.
  • Malmierca MG, Pérez-Victoria I, Martín J, Reyes F, Méndez C, Salas JA, Olano C. (2020). New Sipanmycin Analogues Generated by Combinatorial Biosynthesis and Mutasynthesis Approaches Relying on the Substrate Flexibility of Key Enzymes in the Biosynthetic Pathway. Applied and Environmental Microbiology 86(3):e02453-19.
  • Becerril A, Perez-Victoria I, Ye S, Brana AF, Martin J, Reyes F, Salas JA, Mendez C. (2020). Discovery of Cryptic Largimycins in Streptomyces Reveals Novel Biosynthetic Avenues Enriching the Structural Diversity of the Leinamycin Family. ACS Chemical Biology 15 (6): 1541-1553.
  • Zabala D, Song LJ, Dashti Y, Challis GL, Salas JA, Mendez C. (2020). Heterologous reconstitution of the biosynthesis pathway for 4-demethyl-premithramycinone, the aglycon of antitumor polyketide mithramycin. Microbial Cell Factories 19(1). 111.
  • Becerril A, Álvarez S, Braña AF, Rico S, Díaz M, Santamaría RI, Salas JA, Méndez C. (2018). Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches. PLoS One. 24;13(5):e0198145.
  • Ye S, Braña AF, González-Sabín J, Moris JF, Olano C, Salas JA, Méndez C. (2018). New insights into the biosynthesis pathway of polyketide alkaloid argimycins P in Streptomyces argillaceus. Frontiers in Microbiology 9:252.
  • Malmierca MG, Pérez-Victoria I, Martín J, Reyes F, Méndez C, Olano C, Salas JA. (2018). Cooperative involvement of glycosyltransferases in the transfer of aminosugars in the biosynthesis of the macrolactam sipanmycin by Streptomyces sp. CS149. Applied and Environmental Microbiology 84 (18) e01462-18.
  • Núñez LE, Nybo SE, González-Sabín J, Pérez M, Menéndez N, Braña AF, Shaaban KA, He M, Morís F, Salas JA, Rohr J, Méndez C. (2012). A novel mithramycin analogue with high antitumor activity and less toxicity generated by combinatorial biosynthesis. J Med Chem. 55(12):5813-25.


Name Position E-mail Phone
Carmen Méndez Fernández Group leader cmendezf@uniovi.es 985 103 558
Carlos Olano Álvarez Group leader olanocarlos@uniovi.es 985 105 288
Gloria Blanco Blanco Staff scientist gbb@uniovi.es 985 103 205
Mónica Gómez Malmierca Postdoctoral fellow gomezmonica@uniovi.es 985 105 288
Lorena Cuervo del Pozo cuervolorena@uniovi.es 985 105 288
Miriam Rodríguez García Postdoctoral fellow miroga03@hotmail.com 985 105 287
Laura Prado Alonso Predoctoral fellow laura-prado@outlook.com 985 105 288
Coral García Gutiérrez Predoctoral fellow coral93@hotmail.es 985 105 287
María Soledad González Moreno Predoctoral fellow msol95gm@gmail.com 985 105 287
Leire Peña Noval Technician penaleire@uniovi.es 985 105 287