Sílvia Osuna

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

Marc Garcia-Borràs

Postdoc (BP)

- S. Osuna

PhD and MACMoM students

Carla Calvó

PhD Student

- S. Osuna

Cristina Duran

PhD Student (FPI)

- S. Osuna

Jordi Soler

PhD Student (FPU)

- S. Osuna
- M. Garcia-Borràs

Lorenzo d’Amore

PhD student (IF-UdG)

- S. Osuna
- M. Swart

Miguel Àngel María Solano

PhD student (FPI)

- S. Osuna
- M. Swart

Miquel Estévez

PhD student

- S. Osuna

Eila Serrano

PhD student (FI)

- S. Osuna

Guillem Casadevall

PhD Student

- S. Osuna


ERC Projects. ERC Starting Grants

Project: Network models for the computational design of proficient enzymes (NETMODEZYME)
Researcher: Dr Sílvia Osuna
Reference: ERC-2015-StG-679001
Funding: 1.445.587 €
Period: 01/05/2016 – 30/04/2021

MCIU Proyectos I+D

Project: Evolución Computacional de Enzimas mediante la Exploración de la Superficie Conformacional
Researcher: Sílvia Osuna
Reference: PGC2018-102192-B-100
Funding: 118.580 €
Period: 01/01/2019 – 31/12/2021

MCIU Proyectos I+D. Juan de la Cierva

Project: Juan de la Cierva – Incorporación
Researcher: Dr. Javier Iglesias
Reference: IJCI-2017-34129
Funding: 64.000 €
Period: 01/05/2019 – 30/04/2021

AGAUR. Suport a grups de recerca.

Project: Laboratori de Bioquímica Computacional: Disseny Racional de Nous Enzims (CompBioLab)
Researcher: Dr. Sílvia Osuna
Reference: 2017 SGR 1707
Funding: 10.000 €
Period: 01/01/2017 – 31/12/2020

RES Projects

Project: Computational characterization of reactive intermediates for the discovery and design of new biocatalytic activities: unnatural oxidation catalytic pathways in P450s
Researcher: Dr. Marc García Borràs
Reference: QSB-2019-3-0009
Assigned Hours (in thousands): 65,66


Sílvia Osuna receives Catalonian National Research Award for Young Talent

At this moment is taking place at the Palau de la Generalitat in Barcelona

Mutational analysis of LinD suggests transformations are catalyzed using non-covalent mechanisms

The interconversion of non-activated alkenes and alcohols, catalysed by (de)hydratases, has great potential

Predicting distal active site mutations in computational enzyme design

Many computational enzyme design approaches have been developed in recent years that focus

Enzyme powered micro/nanomotors

Enzyme powered micro/nanomotors have great potential applications in various areas, especially in the