Osuna, Sílvia

Computational design of proficient enzymes: exploring the molecular basis of biocatalysis

Contact info:
Dr. Sílvia Osuna
Tel. (+34) 972 41 93 21


Selected publications

Miguel A. Maria-Solano, Javier Iglesias-Fernández, Sílvia Osuna
Deciphering the Allosterically Driven Conformational Ensemble in Tryptophan Synthase Evolution
J. Am. Chem. Soc., 2019, 141, 13049-13056
DOI: 10.1021/jacs.9b03646

Christian Curado-Carballada, Ferran Feixas, Javier Iglesias-Fernández, Sílvia Osuna
Hidden Conformations inAspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency
Angew. Chem. Int. Ed., 2019, 58, 3097-3101
DOI: 10.1002/anie.201812532

Xi Chen, Hongliu Zhang, Miguel A. Maria-Solano, Weidong Liu, Juan Li, Jinhui Feng, Xiangtao Liu, Sílvia Osuna, Rey-Ting Guo, Qiaqing Wu, Dunming Zhu, Yanhe Ma
Efficient reductive desymmetrization of bulky 1,3-cyclodiketones enabled by structure-guided directed evolution of a carbonyl reductase
Nat Catal, 2019, 2, 931-941
DOI: 10.1038/s41929-019-0347-y

Xavier Arqué, Adrian Romero-Rivera, Ferran Feixas, Tania Patiño, Sílvia Osuna, Samuel Sánchez
Intrinsic enzymatic properties modulate the self-propulsion of micromotors
Nat Commun, 2019, 10, 2826
DOI: 10.1038/s41467-019-10726-8

Antonia Tomás-Loba, Elisa Manieri, Bárbara González-Terán, Alfonso Mora, Luis Leiva-Vega, Ayelén M. Santamans, Rafael Romero-Becerra, Elena Rodríguez, Aránzazu Pintor-Chocano, Ferran Feixas, Juan Antonio López, Beatriz Caballero, Marianna Trakala, Óscar Blanco, Jorge L. Torres, Lourdes Hernández-Cosido, Valle Montalvo-Romeral, Nuria Matesanz, Marta Roche-Molina, Juan Antonio Bernal, Hannah Mischo, Marta León, Ainoa Caballero, Diego Miranda-Saavedra, Jesús Ruiz-Cabello, Yulia A. Nevzorova, Francisco Javier Cubero, Jerónimo Bravo, Jesús Vázquez, Marcos Malumbres, Miguel Marcos, Sílvia Osuna & Guadalupe Sabio
p38Υ is essential for cell cycle progression and liver tumorigenesis
Nature, 2019, 568, 557-560
DOI: 10.1038/s41586-019-1112-8

+ Publications

Dr. Sílvia Osuna

Dr. Osuna obtained her PhD with academic honors in 2010 at the University of Girona (Spain), and moved to the University of California, Los Angeles (USA) with a Marie Curie International Outgoing Fellowship (IOF). She obtained a JdC postdoctoral contract at the UdG, a 5-year RyC contract (RYC-2014-16846), and recently an ICREA Research position.

The group of Dr. Osuna was established as an independent team after she was awarded a Career Integration Grant (CIG, DIREVENZYME 2013-CIG-630978), and an ERC Starting Grant in 2015 (Network Models for the computational design of proficient enzymes, NetMoDEzyme, ERC-2015-StG-679001). The CompBioLab group has recently been recognized at the Catalan level as a new emergent research group (2017 SGR 1707). She is also the PI of a Spanish R+D project (CTQ2014-59212/BQU), and the project associated to her Ramón y Cajal contract (RYC-2014-16846).

Last year, she was awarded the Young Researcher award by the Royal Spanish Society of Chemistry (RSEQ 20116), and the Research award by the Fundación Princesa de Girona (FPdGi 2016- Science category). She also received a special mention by ANQUE (Asociación Nacional de Químicos Españoles) at the European Young Chemistry Awards at EuChemS 2016, and the Young research award by EuroJOC.

Research overview

Billions of years of evolution have made enzymes superb catalysts capable of accelerating reactions by several orders of magnitude. The underlying physical principles of their extraordinary catalytic power still remains highly debated, which makes the alteration of natural enzyme activities towards synthetically useful targets a tremendous challenge for modern chemical biology. The routine design of enzymes will, however, have large socio-economic benefits, as because of the enzymatic advantages the production costs of many drugs will be reduced and will allow industries to use environmentally friendly alternatives. The goal of our group is to make the routine design of proficient enzymes possible.

Billions of years of evolution have made enzymes superb catalysts capable of accelerating reactions by as many as seventeen orders of magnitude. This rate acceleration is achieved by decreasing the activation barriers of reactions, making them possible at lower temperatures and pressures. Enzymes (i.e. biocatalysts) are indeed the most efficient, specific and selective catalysts known. They operate under biological conditions, are biodegradable, non-toxic, their high selectivities and efficiencies reduce the number of work- up steps, and provide product in higher yields. These characteristics make enzyme-catalyzed processes an attractive alternative for chemical manufacturing. However, the use of enzymes in industry is limited, as most of processes do not present a biocatalyst to catalyze and accelerate the corresponding reactions. The ability of routinely designing enzymes for any target process will have large socio-economic impacts, as the production costs of many drugs will be reduced and will allow industries to use environmentally friendly alternatives. However, the routine design of enzymes for any target reaction has not yet been achieved. This is in part motivated by the imprecise knowledge of the underlying physical principles of biocatalysis, which makes the alteration of the natural activity of enzymes towards synthetically relevant targets a tremendous challenge for biochemistry. Current computational and experimental approaches are able to confer natural enzymes new functionalities but are economically unviable and the catalytic efficiencies lag far behind their natural counterparts.

We work in the design of new enzymes for distinct processes important for their potential applications in medicine. We explore the structural basis of improved catalysis achieved by the experimental directed evolution (DE) technique through computational modeling, and are currently developing a new computational protocol based on Molecular Dynamics and network models that reduce the complexity of the enzyme design paradigm. Our computational predictions are tested in the lab to finally elucidate the potential of this genuinely new computational approach for mimicking Nature’s rules of evolution.
We collaborate with many groups, being the most relevant ones: Prof. K. N. Houk (UCLA, USA), Prof. Y. Tang (UCLA, USA), Dr. G. Huisman (Codexis).


We additionally work on the computational exploration of the chemical reactivity and properties of carbon-based materials. This topic is related to Dr. Osuna’s PhD thesis and she has collaborations with the groups of Prof. L. Echegoyen (UTEP), Dr. Y. Yamakoshi (ETH Zurich), Prof. J. M. Poblet (URV), and Prof. N. Martín (UCM).


Principal Investigator

Sílvia Osuna

ICREA Research Professor

Staff and Postdocs

Christian Curado


- S. Osuna

Eduard Masferrer


- S. Osuna

Miquel Estévez


- S. Osuna

Ram Mahato

Postdoc (HFSP)

- S. Osuna

PhD and MACMoM students

Akram Doustmohammadi

PhD student

- S. Osuna

Cristina Duran

PhD Student (FPI)

- S. Osuna

Esther Pruna

PhD student

- S. Osuna

Janet Sánchez

PhD (FPI) student

- S. Osuna

Javier Moreno

PhD student

- S. Osuna

Jonnely Rissell Luizaga

PhD student

- S. Osuna

Guillem Casadevall

PhD Student

- S. Osuna



Project: Fast yet accurate routine rational design of novel enzymes (FASTEN)
Researcher: Dr. Sílvia Osuna
Reference: ERC-2022-CoG-101088032
Funding: 1.996.250 €
Period: 01/10/2023 – 30/09/2028
Project: Computational design of industrial enzymes for green chemistry (GREENZYME)
Researcher: Dr. Sílvia Osuna
Reference: ERC-2022-PoC2-101112805
Funding: 150.000 €
Period: 01/05/2023 – 31/10/2025

MCIU Proyectos I+D

Project: Evolución computacional de nuevos (bio)catalizadores
Researcher: Dr. Sílvia Osuna
Reference: PDC2022-133950-100
Funding: 143.750 €
Period: 01/12/2022 – 31/12/2024
Project: Diseño computacional de enzimas conformacionalmente dirigido para mejorar la actividad aislada o en complejo
Researcher: Dr. Sílvia Osuna
Reference: PID2021-129034NB-100
Funding: 157.300 €
Period: 01/09/2022 – 31/08/2025

AGAUR. Suport a grups de recerca.

Project: Theoretical Chemistry of Biosystems (TCBioSys)
Researcher: Dr. Sílvia Osuna
Reference: 2021 SGR 00487
Funding: 60.000 €
Period: 01/01/2022 – 31/12/2024


Project ID: UMA-2023-3
Title: Exloring the versatility of squalene-hopene cyclase
Assigned hours: 5.800.000
IP’s: Dr. Sílvia Osuna
Period: 01/11/2023 – 28/02/2024

Other projects

Researcher: Dr. Sílvia Osuna
Funding: 77.464 €
Period: 2023-2024


Nobu TokurikiUniversity of British Columbia (Canada), collaboration with Sílvia Osuna.
Manfred ReetzMax-Planck-Institut für Kohlenforschung (Germany), collaboration with Sílvia Osuna.

Girona Seminar 2024

During this week (May 28-31) there is the main event of the year: #GirSem24 at

2024, International Women’s Day – Women’s IQCC Forum

8th of March is International Women’s Day.  The IQCC has currently a rather

Sílvia Osuna granted a new ERC Proof of Concept grant

Prof. Sílvia Osuna, ICREA Professor at the Institute of Computational Chemistry and Catalysis

Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases

The interconversion of monoterpenes is facilitated by a complex network of carbocation rearrangement