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

Adrian Romero-Rivera, Marc Garcia-Borràs and Sílvia Osuna
Computational tools for the evaluation of laboratory-engineered biocatalysts
Chem. Commun. 2017, 53, 284-297
DOI: 10.1039/C6CC06055B

Miguel A. Maria-Solano, Adrian Romero-Rivera and Sílvia Osuna
Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase
Org. Biomol. Chem. 2017, 15, 4122 – 4129
DOI: 10.1039/C7OB00482F

Sílvia Osuna, Gonzalo Jiménez-Osés, Elizabeth L. Noey, and K. N. Houk
Molecular Dynamics Explorations of Active Site Structure in Designed and Evolved Enzymes
Acc. Chem. Res. 2015, 48, 1080-1089.
DOI: 10.1021/ar500452q

Gonzalo Jiménez-Osés, Sílvia Osuna, Xue Gao, Michael R Sawaya, Lynne Gilson, Steven J Collier, Gjalt W Huisman, Todd O Yeates, Yi Tang, and K N Houk
The Role of Distant Mutations and Allosteric Regulation on Active Site Dynamics and Catalysis
Nature Chem. Biol. 2014, 10, 431-436.
(†: The authors have equally contributed to the work)
DOI: 10.1038/nchembio.1503

Maira R. Cerón, Marta Izquierdo, Marc Garcia-Borràs, Sarah S. Lee, Steven Stevenson, Sílvia Osuna, and Luis Echegoyen
Bis-1,3-Dipolar Cycloadditions on Endohedral Fullerenes M3N@Ih-C80 (M = Sc, Lu): Remarkable Endohedral-Cluster Regiochemical Control
J. Am. Chem. Soc. 2015, 137, 11775–11782.
DOI: 10.1021/jacs.5b07207

+ 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, and has recently been awarded a 5-year RyC contract (RYC-2014-16846).

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). 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.

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


Staff and Postdocs

Ferran Feixas

Postdoc (MSCA-IF)

Javier Iglesias

Postdoc (MSCA-IF)

Marc Garcia-Borràs

PhD and MACMoM students

Adrià Romero

PhD student (FI)

- S. Osuna
- M. Swart

Christian Curado

PhD student

- S. Osuna

Lorenzo d’Amore

PhD student

- 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


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: 1.400.000 €
Periode: 2016 – 2020

Marie Skłodowska-Curie Actions. Marie Curie Career Integration Grant (CIG)

Project: Computational Exploration of Directed Evolution rules for turning enzymatic activities (DIREVENZYME)
Researcher: Dr. Sílvia Osuna
Reference: PCIG14-GA-2013-630978
Funding: 100.000 €
Periode: 2014 – 2018

MINECO Projects. Proyectos I+D

Project: Spin state and enzymatic catalysis based on bottom-up computational design (SPINENZYMECAT)
Researcher: Dr Marcel Swart & Dr Sílvia Osuna
Reference: CTQ2014-59212-P
Funding: 116.160 €
Periode: 2015 – 2017

MINECO Projects. Ramon y Cajal

Project: Programa Ramón y Cajal
Researcher: Dr. Sílvia Osuna
Reference: RYC-2014-16846
Funding: 308.600 €
Periode: 2016 – 2020


Sílvia Osuna wins the FPdGi Recerca Científica Award 2016

Sílvia Osuna Oliveras (Castelló d’Empúries, 1983), researcher of the Institut de Química Computacional

Sílvia Osuna awarded ERC Starting Grant

Dr. Sílvia Osuna has been awarded a ‘ERC Starting Grant’ (ERC-StG-2015-679001) grant for

Sílvia Osuna wins RSEQ Young Researcher Award

Sílvia Osuna has been awarded one of the four Young Researcher awards given

Marie Curie IF fellowship awarded to Javier Iglesias and Sílvia Osuna

The Marie Curie IF project named EnzVolNet (H2020-MSCA-IF-2016-753045) has been selected for funding