BIOTEC 2010

El Congreso Científico BIOTEC 2010, organizado por la Sociedad Española de Biotecnología (SEBIOT), continuará con la tradición de ediciones anteriores, atrayendo a los mejores profesionales, investigadores y estudiantes del área biotecnológica.

Investigadores de instituciones públicas y privadas de instituciones locales, nacionales e internacionales elaborarán un completo programa de ponencias presentando los últimos avances, tendencias y procesos del sector, complementado con una sesión de posters.

Persona de contacto: Sra. Laura Hernández (e-mail: sebiot@csic.es)

http://www.sebiot.org

http://www.biospain2010.org

PROGRAMA BIOTEC2010

Infórmese de los Seminarios satélites en los días previos

DÍA 29 DE SEPTIEMBRE

08:00 - 09:00 Registro

09:00 - 09:30 Bienvenida Biotec 2010

9h30. Nuevos retos terapéuticos y terapias avanzadas (Sala Luneta A)

Moderadores: Dra. Carmen Castresana (CNB-CSIC) y Dr. José Luis Martínez (CNB-CSIC)

Ponentes:

Dr. José López Barnéo, (Universidad de Sevilla). "Cell therapy in parkinson's disease"

Dr. Angel Garcia Martin, (Inbiomed). “Cancer stem cells as therapeutic targets”.

Dr. Antonio Bernard, (CNIC). "Clinical aplications of adult mesenchimal item cells: biosafety implications".

Dr. Gabriel Márquez, (Genetrix). "Stem cells: a new panacea for medicine?".

9h30. Ingeniería Metabólica y nuevos productos (Sala Luneta B)

Moderadores: Dr. Jose Luis García López (CIB-CSIC) y Dra. Paloma Liras (Universidad de León)

Ponentes:

Dr. Juan Francisco Martín, (Universidad de León). "The proteome and secretome of P. chrysogenum: from penicilin to white biotechnology".

Dr. Pau Ferrer, (Universidad Autónoma de Barcelona). "Improving recombinant protein production in Pichia Pastoris through metabolic engineering".

Dr. José Luis Revuelta, (Universidad de Salamanca/CSIC). "Cell factories for vitamins production".

Dra. Carmen Vargas, (Universidad de Sevilla). "Ectoines: applications, synthesis, regulation, and biotechnological production".

11:30 - 12:00 Sesión de Posters y Coffee-Break

13:30 - 14:00 Sesión de Posters

14:00 - 15:30 Comida

15h30. Tecnologías Diagnósticas y Modelos Animales (Sala Luneta A)

Moderadores: Dr. Ignacio López Goñi (Universidad de Navarra) y Dra. Carmen Vela (Ingenasa)

Ponentes:

Dra. Fátima Bosch, (Universidad Autónoma de Barcelona). "Gene Therapy Approaches for Mucopolisaccharidosis Type IIIA: from a Mouse Model to a clinical trial".

Dra. Maite Mujika, (CIC Microgune). “New biosensing estrategies based on immunomagnetic microdevices”.

Dr. Luis Enjuanes, (CNB-CSIC). "Coronavirus expresion vectors, transcription mechanisms and protection against SARS-CoV".

15h30. Biotecnología Ambiental (Sala Luneta B)

Moderadores: Dr. Francisco Omil (Universidad de Santiago de Compostela) y Dr. Fernando Rojo (CNB-CSIC)

Ponentes:

Dr. Juan Luís Ramos, (Estación Experimental del Zaidín-CSIC). “Pseudomonas putida dot-t1e is an extremophile useful for relevant biotechnological applications".

Dr. Ramón Méndez Pampin, (Universidad de Santiago de Compostela) “Advanced biotechnologies for the renoval of nutrients”.

Dr. Iñaki Tejero Monzón, (Universidad de Cantabria). “Application of hybrid biological reactors for the enhancement of existing sewage treatment plants”.

17:30 - 18:00 Sesión de Posters y Coffee-Break

18:00 - 19:30 Asamblea General de SEBIOT (Sala de Cámara)

DÍA 30 DE SEPTIEMBRE

9h00. Mesa redonda: Nanobiotecnología (Sala Luneta A)

Moderadores: Dr. José Mª Carazo (CNB-CSIC) y José Fernando Morán Juez (Agrobiotechnology Institute, UPNA-CSIC-Government of Navarra)

Dra. Elena Ferapontova, (Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Dinamarca). ”Stabilisation and activation of enzymes at electrodes for biosensor and biofuel cell development”.

Dra. María José Hernáiz, (Universidad Complutense, Madrid). "Surface plasmon resonance as a tool to study carbohydrate-protein interactions".

Dr. Jaime García-Rupérez, (Centro de Tecnología Nanofotónica, Universidad Politécnica de Valencia). "A highly integrated optical sensor for point of care label free identification of pathogenic bacteria strains and their antibiotic resistance (IPTOSENS)".

Dr. Josep Samitier, (Instituto de Bioingeniería de Cataluña). "A study of cell-substrate interactions on polymer Micro-nanopatterned substrates."

9h00. Mesa redonda: Bacterias lácticas

Moderadores: Dr. Gaspar Pérez (Instituto de Agroquímica y Tecnología de los Alimentos-CSIC) y Dra. Paloma López (CIB-CSIC)

Ponentes:

Dr. Juan Miguel Rodríguez, (Universidad Complutense de Madrid).”Nuevos criterios para la selección de probióticos a la carta".

Dr. Gaspar Pérez Martínez, (Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia) ”Los probióticos como fuente de moléculas con actividad biológica”

Dr. José Luis Ruiz Barba, (Instituto de la Grasa, CSIC/CIAL, Sevilla). ”Procesos moleculares para la mejora de productos lácteos" .

10:30 - 11:00 Sesión de Posters y Coffee-Break

11h00. Ómicas y Biotecnología de Sistemas (Sala Luneta B)

Moderadores: Dr. Fernando Corrales (CIMA-Universidad de Navarra) y Dr. Manuel Cánovas (Universidad de Murcia)

Ponentes:

Dr. Jeffrey Green, (The Krebs Institute, Departamento de Biología y Biotecnología, Universidad de Sheffield, Reino Unido). "SUMO: Systems Understanding of Microbial Responses to Oxygen".

Dr. Nestor Torres, (Universidad de La Laguna). "A system biotechnological virtuous circle: from proteome, metabolome and signalome to "modelome", transcriptome and optimization. Application to the overproduction of succinate and l-carnitine in E.coli in salt stress conditions".

Dra. Marta Cascante, (Universidad de Barcelona). "Detecting metaboic flux alterations associated to multifactorial diseases: application to target discovery".

11h00. Biotecnología Alimentaria (Sala Luneta A)

Moderadores: Dra. Blanca Bermejo (Laboratorio Dr. Echevarne) y Dr. Mario Díaz (Universidad de Oviedo)

Ponentes:

Dr. Andreu Palou, (Universidad de las Islas Baleares). "Nutrigenomics and obesity. Perspectives for the European health claims on food".

Dr. Alfredo Martínez, (Universidad de Navarra). "Biotechnology and personalized nutrition".

14:00 - 15:30 Comida

15h30. Bioinformática (Sala Luneta B)

Moderadores: Dr. Juan Luis Ramos (Estación Experimental del Zaidín-CSIC) y Dr. Andrés Alcántara (Universidad Complutense de Madrid)

Ponentes:

Dr. Víctor Segura, (CIMA-Universidad de Navarra). "Signal processing of genomic and proteomic signals".

Dr. Rubén Nogales Cadenas, (Universidad Complutense). "Modular analysis of gene sets: beyond enrichment to discover functional associations".
Dr. Sylvain Foissac, (Integromics). "RNA-seq data analysis provides evidence for a new molecular mechanism generating antisense transcripts in human cells".

15h30. Biocombustibles (Sala Luneta A)

Moderadores: Dr. Juan José Rubio (INBIOTEC-León) y Dr. Juan Luis Serra (Universidad del Pais Vasco)

Ponentes:

Dr. Philippe Soucaille, (Metabolic Explorer. Biopole Clermont-Limagne. Francia).

Dr. Emilio Molina, (Universidad de Almería). "Development of a process of microalgal biofuel".

Dra. Mª Jesús Martínez, (CSIC). "Fungal laccases: role in the second generation bioethanol production".

17:30 - 18:00 Sesión de Posters y Coffee-Break

18h00. Mesa redonda: Integrando Europa y Latinoamérica en la Bio-economía basada en el conocimiento.

Moderadores: Dr. Carlos Malpica (BioEuroLatina) y Dr. Francisco Ferrándiz (SEBIOT)

Ponentes:

Dr. Carlos Malpica, (BioEuroLatina) y Dr. Francisco Ferrándiz, (SEBIOT). "Conclusiones y seguimientos de EULAFF".

Dr. Victor Villalobos, (IICA) y Dr. Albert Sasson, (BioEuroLatina). "Programa IICA para biotecnología en LA".

Dr. Antonio Díaz, (PCM) y Fidel Rodríguez, (Bioaurum/BioEuroLatina). "Parques Científicos - Clusters Tecnológicos".

Dr. José Luís Solleiro, (Universidad Nacional Autónoma de México). "Colaboraciones Europa-México).

Dr. Alberto Díaz, (Instituto Nacional de Tecnología Industrial, Argentina). "Colaboraciones Europa-Argentina".

Dr. Jose Manuel Leceta, (CDTI). "Iberoamérica Innova".

18h00. Mesa redonda: Ciencia y Biotecnología en Navarra

Moderador: Dr. Iñigo Lasa, (Universidad Pública de Navarra, Instituto de Agrobiotecnología).

Ponentes:

Dr. Ignacio Melero, (CIMA y Clínica Universitaria de Navarra).

Dr. Felipe Prosper, (Clínica Universitaria de Navarra). "Células madre en terapia".

Dr. Javier Pozueta, (CSIC, Instituto de Agrobiotecnología). "Ten years of starch biotechnology in Navarre".

Dr. José Fernando Morán, (Universidad Pública de Navarra, Instituto de Agrobiotecnología)."Use of recombinant Fe-superoxidem dismutase to search for anti-nitrative antioxidants".

Dr. Dámaso Molero, (3P Biopharmaceuticals).

Dr. Ernesto Bravo, (FIDENA)

DÍA 1 DE OCTUBRE

9h00. Biotecnología vegetal (Sala Luneta B)

Moderadores: Dr. Cesar Arrese-Igor (UPNA) y Dr. Antonio Leyva (CNB-CSIC)

Ponentes:

Dr. Changfu Zhu, (Universidad. de Lleida). "Advances in multi gene engineering for the production of valuable plant metabolites".

Dr. José Miguel Martínez Zapater, (CNB-CSIC). "The impact of grapevine genomics on viticulture: challenges and possibilities."

Dr. Emilio Rodriguez Cerezo, "Beyond transgenics: new biotechnologies in plant breeding".

9h00. Biocatálisis (Sala Luneta A)

Moderadores: Dr. José Mª Sánchez-Montero (Universidad Complutense de Madrid ) y Dra. Isabel de la Mata (Universidad Complutense de Madrid).

Conferenciantes:

Dr. Antonio Ballesteros, (Instituto de Catálisis y Petroquímica-CSIC). "Biocatalysis: a personal project at the CSIC".

Dr. Ramón Canela, (Universidad de Lleida). "Taking advantage of the biocatalytic activity of fungal resting cells".

Dr. Pere Clapés, (Instituto de Química Avanzada de Cataluña-CSIC). "Enzyme Catalyzed Asymmetric Aldol Additions: Carbohydrates and iminosugars from DHAP to unphosphorylated donor analogues".

11:00 - 11:30 Sesión de Posters y Coffee-Break

11:30 - 12:30 Clausura de Biotec 2010

13:30 - 14:00 Clausura de Biospain 2010 (Sala Principal)

Conferencia Plenaria del Prof. J.V. Sinisterra en el 3rd EuCheMS Chemistry Congress

Molecular Life Sciences
(Biostructure, Biopolymers and their Conjugates, Medicinal Chemistry, Biocatalysis and Biomaterials, Impact of Analytical Chemistry in Life/Bio Sciences)

Plenary Speaker: Barbara Imperiali (USA)
Fluorescent Tools for Chemical Biology

Biostructure, Biopolymers and their Conjugates
Convener: Juan Fontecilla-Camps (FR)
Invited Speakers:

Rolf Thauer (DE)

The Structure of the Nickel Enzyme that Catalyzes the Anaerobic Oxidation of Methane in Archaea
Dino Moras (FR)
Allosteric Control of Dimerisation in Nuclear Receptors of Hormones
Eric Westhof (FR)
RNA Modules and the Assembly of RNA Architecture
Rebecca Wade (DE)
Simulation and Design of Dynamic Tunnels in Enzymes
Péter Tompa (HU)
Intrinsically Disordered Proteins in Cellular Function and Disease
Yoshihito Watanabe (JP)
Design of Organometallo-Enzymes

Medicinal Chemistry
Convener: Roberto Pellicciari (IT)
Invited Speakers:

Maria Flocco (UK)

Biophysical Methods in Medicinal Chemistry Design
Tudor I. Oprea (USA)
The Art of Mapping Drug-Target Interactions
Gisbert Schneider (DE)
Molecular Design Patterns
Maurizio Botta (IT)
Design and Synthesis of HIV-1 Inhibitors
Rasmus Clausen (DK)
Development of Specific Glutamate Receptor Ligands
Timothy M. Willson (USA)
Open Access Chemical Probes

Biocatalysis and Biomaterials
Convener: Manfred Reetz (DE)
Invited Speakers:

Alan Berry (UK)

Novel Enzymes Based on an Aldolase Scaffold
Uwe T. Bornscheuer (DE)
Protein Engineering Tools for Enantioselective Biocatalysis
Donald Hilvert (CH)
Designer Enzymes
Dick B. Janssen (NL)
Engineered Dehalogenases in Enantioselective Biocatalysis
José Vicente Sinisterra (ES)
Industrial Biotransformations in Green Solvents
Pierre Monsan (FR)
Molecular Engineering of a Transglucosidase for the Catalysis of Specific Synthesis

Impact of Analytical Chemistry in Life/Bio Sciences
Convener: Jeremy Nicholson (UK)
Invited Speakers:

R. Graham Cooks (USA)

Applications of Desorption Electrospray Ionisation
Paul Thomas (UK)
Breath Analysis for Disease Diagnosis
Frank Breitling (DE)
Applications of High Density Peptide Arrays in Cancer Studies
Fred Regnier (USA)
Protein Biomarkers of Oxidative Stress
Jeremy Nicholson (UK)
Statistical Spectroscopic Approaches in Systems Biology and Medicine

Pace et al, Green Chemistry 2010

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

Vittorio Pace, Pilar Hoyos, María Fernández, José V. Sinisterra and Andrés R. Alcántara
Green Chem., 2010, 12, 1380-1382

Abstract

An efficient chemoselective nitrogen functionalization of phthalimides by using KF-Alumina in 2-methyltetrahydrofuran, a solvent obtained from renewal sources, is described.

http://dx.doi.org/10.1039/c0gc00113a

Pace et al, Journal Organic Chemistry 2010

Improved Arndt-Eistert Synthesis of alpha-Diazoketones Requiring Minimal Diazomethane in the Presence of Calcium Oxide as Acid Scavenger.

V. PACE, G. VERNIEST, J.V. SINISTERRA, A.R. ALCANTARA, N. DE KIMPE

Abstract

A practical methodology to obtain α-diazoketones through an improved Arndt−Eistert synthesis is described. The method allows the efficient transformation of acid halides using a stoichiometric amount of diazomethane in the presence of calcium oxide, without concomitant ketene or haloketone formation. The obtained α′-brominated-α-diazoketones were employed as suitable substrates for the synthesis of interesting α-arylamino-α′-halomethylketones.

http://dx.doi.org/10.1021/jo101105g

Pace et al, Synthesis 2010

First General Route to Substituted α-Arylamino-α′-chloropropan-2-ones by Oxidation of N-Protected Aminohalohydrins: The Importance of Disrupting Hydrogen Bond Networks

Vittorio Pace, Álvaro Cortés Cabrera, María Fernández, José V. Sinisterra, Andrés R. Alcántara

Abstract

The presence of a network of intra- and intermolecular hydrogen bonds in β-arylamino alcohols, confirmed by both IR spectroscopy and computer modeling, inhibits their oxidation to the corresponding α-amino ketones. A straightforward protocol, including highly regioselective protection (as carbamates) and subsequent oxidation with Dess-Martin periodinane, affords near quantitative yields of the desired N-protected ketones, which upon mild treatment with iodotrimethylsilane leads to a series of differently functionalized α-arylamino-α′-chloro ketones.

http://dx.doi.org/10.1055/s-0030-1257938

A.R. Alcántara, J.M. Sanchez-Montero, An. R. Acad. Nac. Farm., 2010

Hydrolases use in the preparation of drugs and homochiral intermediates

Andrés R. Alcántara León, José María Sánchez Montero

Abstract

The excellent regio and steroselectivity of biocatalysts, combined with their environmental friendly behaviour, make possible to carry out under biocatalytical conditions many processes which, conducted on strictly classical methodologies, would demand expensive and tedious protection and de-protection steps. In this work we review some examples in which hydrolases (the most useful enzymes in the Biotransformations field) catalyse different reactions for synthesizing only the therapeutically essential stereoisomer of different homochiral building blocks for drugs. Thus, processes leading to antiviral, anticancer, antihypertensive or antiinflammatory drugs, along with many others, are described, remarking the versatility and utility of the biocatalysts in the above-mentioned processes.

http://www.analesranf.com/index.php/aranf/article/view/1091

Iterative Saturation Mutagenesis Accelerates Laboratory Evolution of Enzyme Stereoselectivity: Rigorous Comparison with Traditional Methods

Iterative Saturation Mutagenesis Accelerates Laboratory Evolution of Enzyme Stereoselectivity: Rigorous Comparison with Traditional Methods

Manfred T. Reetz*†, Shreenath Prasad†, José D. Carballeira‡, Yosephine Gumulya† and Marco Bocola§

Max-Planck-Institut fr Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mlheim an der Ruhr, Germany, Industrial Biotransformations Service, Madrid Science Park, C/Santiago Grisola 2, Tres Cantos, 28760 Madrid, Spain, and Institut fr Biophysik und Physikalische Biochemie, Universitt Regensburg, Universittsstrasse 31, 93053 Regensburg, Germany

Abstract

Efficacy in laboratory evolution of enzymes is currently a pressing issue, making comparative studies of different methods and strategies mandatory. Recent reports indicate that iterative saturation mutagenesis (ISM) provides a means to accelerate directed evolution of stereoselectivity and thermostability, but statistically meaningful comparisons with other methods have not been documented to date. In the present study, the efficacy of ISM has been rigorously tested by applying it to the previously most systematically studied enzyme in directed evolution, the lipase from Pseudomonas aeruginosa as a catalyst in the stereoselective hydrolytic kinetic resolution of a chiral ester. Upon screening only 10000 transformants, unprecedented enantioselectivity was achieved (E = 594). ISM proves to be considerably more efficient than all previous systematic efforts utilizing error-prone polymerase chain reaction at different mutation rates, saturation mutagenesis at hot spots, and/or DNA shuffling, pronounced positive epistatic effects being the underlying reason.

http://dx.doi.org/10.1021/ja1030479

Video Institucional - Parque Científico de Madrid - Madrid Science Park

Lactobacillus reuteri 2'-Deoxyribosyltransferase, a Novel Biocatalyst for Tailoring of Nucleosides

J. FERNANDEZ LUCAS, C. ACEBAL, J.V. SINISTERRA, M. ARROYO, I. DE LA MATA

Applied and Environmental Microbiology, 2010, 76, 1462-1470

A novel type II nucleoside 2'-deoxyribosyltransferase from Lactobacillus reuteri (LrNDT) has been cloned and overexpressed in Escherichia coli. The recombinant LrNDT has been structural and functionally characterized. Sedimentation equilibrium analysis revealed a homohexameric molecule of 114 kDa. Circular dichroism studies have showed a secondary structure containing 55% -helix, 10% β-strand, 16% β-sheet, and 19% random coil. LrNDT was thermostable with a melting temperature (Tm) of 64°C determined by fluorescence, circular dichroism, and differential scanning calorimetric studies. The enzyme showed high activity in a broad pH range (4.6 to 7.9) and was also very stable between pH 4 and 7.9. The optimal temperature for activity was 40°C. The recombinant LrNDT was able to synthesize natural and nonnatural nucleoside analogues, improving activities described in the literature, and remarkably, exhibited unexpected new arabinosyltransferase activity, which had not been described so far in this kind of enzyme. Furthermore, synthesis of new arabinonucleosides and 2'-fluorodeoxyribonucleosides was carried out.

http://dx.doi.org/10.1128/AEM.01685-09

Biocatalytic Strategies for the Asymmetric Synthesis of alpha-Hydroxy Ketones

P. HOYOS, J.V. SINISTERRA, F. MOLINARI, A.R. ALCANTARA, P. DOMINGUEZ DE MARIA

Acc. Chem. Res. 2010, 43(2), 288-299.

Biography

Pilar Hoyos was born in Madrid (Spain) in 1980, and she received her B.S. degree in Pharmacy (2003) and Ph.D. in Chemistry (2008) from Complutense University of Madrid. Her ongoing research as a member of the Biotransformations Group inside the Department of Organic and Pharmaceutical Chemistry (Complutense University of Madrid) focuses on the chemoenzymatic synthesis of optically pure secondary alcohols and α-hydroxycarbonyl compounds as chiral building blocks for drugs, mainly by means of hydrolases, lyases, and oxido-reductases.
Josep-Vicent Sinisterra was born in Madrid (Spain) in 1950 and received his B.S. (1972) and Ph.D. (1975) degrees in Chemistry from the University Complutense de Madrid (UCM). He was a postdoctoral fellow (1981−1982) at the Ecole Polytechnique (Toulouse, France), and invited professor in the Enzymatic technology laboratory of CNRS - Marseille (1986−87), and in the Biology Department (University of Warwick (1996). Since 1988, he has been a full professor in Organic & Pharmaceutical Chemistry at the Faculty of Pharmacy (UCM) as well as director of the Biotransformations Group, qualified as a research quality group in Spain. In addition, he is director of Industrial Biotransformations Service, a R+D+i institute in the Parque Cientifico de Madrid. His major research lines are whole-cell-biocatalyzed reactions, preparation of biocatalysts, and chemoenzymatic production of chiral building blocks for drugs and food additive synthesis. He has published more than 260 papers in international journals of Biocatalysis, Biotransformations, and Organic Chemistry.
Francesco Molinari was born in 1961 in Milano, Italy. He received a B.S. in chemistry (1986) under the supervision of Prof. Francesco Sannicol and Ph.D. (1991) under the supervision of Prof. Cesare Gennari. During these years, his fields of interest were organic synthesis applied to problems of molecular recognition, bifunctional catalysis, and stereoselective carbon−carbon formation. He was a postdoctoral fellow at the Instituto Tecnico of Lisbon working on extractive bioconversions with Prof. Joaquim Cabral. He began his independent career at the Industrial Microbiology Section of the Department of Food Science and Microbiology, University of Milano in 1992. Since 2000, he has been Professor of Chemistry and Biotechnology of Fermentations at the University of Milano. Prof. Molinari’s research interests include (stereo)-selective biotransformations, production and isolation of microbial secondary metabolites, and wine fermentations. He has been member of the Scientific Board of the Italian Society of General Microbiology and Microbial Biotechnology (SIMGBM) and of the Italian Association of Biocatalysis and Bioseparations (AIBB).

Andres R. Alcantara was born in C0rdoba (Spain) in 1962 and received his B.S. (1985) and Ph.D. (1989) degrees in Chemistry from the University of Crdoba. He was a postdoctoral fellow at the University of Kent at Canterbury (U.K.) from 1989 to 1991, after which he began his career at the Faculty of Pharmacy, Complutense University of Madrid (Spain), becoming Assistant Professor (permanent position) in 1993. As a member of the Biotransformations Group inside the Department of Organic and Pharmaceutical Chemistry, his major research line is the chemoenzymatic production of chiral building blocks for drug synthesis, working mainly with hydrolases and ketoreductases. After being a member of the Directive Board and Coordinator of the Applied Biocatalysis Group of the Spanish Society of Biotechnology (SEBiot), in 2008 he was appointed its General Secretary.

Pablo Dominguez de Maria was born in Gran Canaria (Spain) in 1974. He received a B.S. in Pharmacy (1997) and a B.S. in Chemistry (2001), and completed his Ph.D. in 2002 in the Faculty of Pharmacy at Complutense University (Madrid). After 2 years at Degussa AG (Germany) as a postdoctoral research scientist (2003−2004), he moved to AkzoNobel BV (The Netherlands) in 2005. Since July 2009, he has worked as Group Leader in the Institute of Technical and Macromolecular Chemistry, RWTH Aachen University (Germany), within the group of Prof. Dr. Walter Leitner. His main scientific interests are (industrially feasible) biocatalytic processes, new trends in white biotechnology, and biomimetic organocatalytic concepts. In 2005, he was awarded the Young Scientist Prize by the Iberoamerican Academy of Pharmacy.

Abstract

The development of efficient syntheses for enantiomerically enriched α-hydroxy ketones is an important research focus in the pharmaceutical industry. For example, α-hydroxy ketones are found in antidepressants, in selective inhibitors of amyloid-β protein production (used in the treatment of Alzheimer’s), in farnesyl transferase inhibitors (Kurasoin A and B), and in antitumor antibiotics (Olivomycin A and Chromomycin A3). Moreover, α-hydroxy ketones are of particular value as fine chemicals because of their utility as building blocks for the production of larger molecules. They can also be used in preparing many other important structures, such as amino alcohols, diols, and so forth. Several purely chemical synthetic approaches have been proposed to afford these compounds, together with some organocatalytic strategies (thiazolium-based carboligations, proline α-hydroxylations, and so forth). However, many of these chemical approaches are not straightforward, lack selectivity, or are economically unattractive because of the large number of chemical steps required (usually combined with low enantioselectivities).
In this Account, we describe three different biocatalytic approaches that have been developed to efficiently produce α-hydroxy ketones:
(i) The use of thiamine diphosphate-dependent lyases (ThDP-lyases) to catalyze the umpolung carboligation of aldehydes. Enantiopure α-hydroxy ketones are formed from inexpensive aldehydes with this method. Some lyases with a broad substrate spectrum have been successfully characterized. Furthermore, the use of biphasic media with recombinant whole cells overexpressing lyases leads to productivities of 80−100 g/L with high enantiomeric excesses (up to >99%).
(ii) The use of hydrolases to produce α-hydroxy ketones by means of (in situ) dynamic kinetic resolutions (DKRs). Lipases are able to successfully resolve racemates, and many outstanding examples have been reported. However, this approach leads to a maximum theoretical yield of 50%. As a means of overcoming this problem, these traditional lipase-catalyzed kinetic resolutions are combined with racemization of remnant substrate, which can be done in situ or in separate compartments. Examples showing high conversions (>90%) and enantiomeric excesses (>99%) are described.
(iii) Whole-cell redox processes, catalyzed by several microorganisms, either by means of free enzymes (applying a cofactor regeneration system) or by whole cells. Through the use of redox machineries, different strategies can lead to high yields and enantiomeric excesses. Some enantiopure α-hydroxy ketones can be formed by reductions of diketones and by selective oxidations of vicinal diols. Likewise, some redox processes involving sugar chemistry (involving α-hydroxy ketones) have been developed on the industrial scale. Finally, the redox whole-cell concept allows racemizations (and deracemizations) as well.
These three strategies provide a useful and environmentally friendly synthetic toolbox. Likewise, the field represents an illustrative example of how biocatalysis can assist practical synthetic processes, and how problems derived from the integration of natural tools in synthetic pathways can be efficiently tackled to afford high yields and enantioselectivities.

http://dx.doi.org/10.1021/ar900196n

Enzyme-catalyzed synthesis of unnatural or modified nucleosides

JOSE VICENTE SINISTERRA; ANDRÉS-RAFAEL ALCÁNTARA; MARCOS ALMENDROS; MARÍA JOSÉ HERNÁIZ; JOSÉ-MARÍA SANCHEZ-MONTERO; JORGE TRELLES

In Wiley Encyclopedia of Industrial Biotechnology. New York, John Wiley and Sons. 2010

Description

Like the first edition, this new edition presents all key aspects, theoretical and practical, of industrial biological processes, techniques, equipment, products, as well as ethical and regulatory issues. The coverage has been expanded to include additional important areas of pharmaceutical and biologics bioprocess technology such as the production of vaccines, biopharmaceuticals and the methods used to manufacture biomaterials – biofabrication—used in microfluidics, tissue engineering, biosensors, bioelectronics, bioarrays and bionanotechnology. The encyclopedia is a key reference for scientists, technologists, and students working in the broad area of industrial biotechnology.

http://eu.wiley.com/WileyCDA/WileyTitle/productCd-0471799300.html

Green glycosylation using ionic liquid to prepare alkyl glycosides for studying carbohydrate–protein interactions by SPR

F. J. MUÑOZ, S. ANDRE, H.J. GABIUS, J.V. SINISTERRA, M.J. HERNAIZ, R.J. LINHARDT

Green Chemistry, 2009, 11, 373 - 379

Abstract

Several simple glycosides of D-glucose (Glc) and N-acetyl-D-galactosamine (GalNAc) were prepared in a single step glycosylation reaction using unprotected and unactivated sugar donors. The resulting GalNAc glycoside, containing a bifunctional linker, was used to immobilize this glycoconjugate to a self assembled monolayer on a gold biosensor chip. Surface plasmon resonance (SPR) experiments demonstrated that this immobilized glycoconjugate bound to GalNAc specific lectin, Viscum album agglutinin.

http://dx.doi.org/10.1039/b814171a

Highly Efficient Synthesis of New alpha-Arylamino-a-chloropropan-2-ones via Oxidative Hydrolysis of Vinyl Chlorides Promoted by Calcium Hypochlorite

V. Pace, F. Martinez, M. Fernandez, J.V. Sinisterra, A.R. Alcantara.
Full Paper
Advanced Synthesis and Catalysis, 2009, 18, 3199-3126.
- Biotransformations Group, Department of Organic and Pharmaceutical Chemistry, Pharmacy Faculty, Complutense University, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain, Fax: (+34)-91-394-1820
- Industrial Biotransformations Service (SBI), Scientific Park of Madrid (PCM), C/Santiago Grisolía 2, 28760 Tres Cantos, Madrid, Spain
Correspondence to Andrés R. Alcántara, Biotransformations Group, Department of Organic and Pharmaceutical Chemistry, Pharmacy Faculty, Complutense University, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain, Fax: (+34)-91-394-1820 email: Andrés R. Alcántara (andresr@farm.ucm.es)
Funded by:
CAM (Comunidad Autónoma de Madrid, QO-UCM); Grant Number: S-0505/PPQ/0344
MEC (Ministerio de Educación y Ciencia); Grant Number: CTQ2006-09052
Ministerio de Ciencia e Innovación; Grant Number: FPU-AP-2005-5112

Keywords
amines • halogenation • ketones • oxidation • protecting groups

Abstract
The oxidative hydrolysis of different trifluoroacetyl-protected N-(2-chloroallyl)anilines, promoted by calcium hypochlorite, is able to yield several not previously described -arylamino--chloropropan-2-ones, very valuable building blocks that are useful as precursors of several drugs, in excellent yields and short reaction times. The main requirement of the reaction for avoiding the undesired aromatic chlorination (N-protection) is effectively solved by the use of the easily formed and removed N-trifluoroacetyl group. Thus, it is possible to perform the oxidative hydrolysis-deprotection step using a one-pot strategy, obtaining quantitative yields in very short reaction times.

http://dx.doi.org/10.1002/adsc.200900565

Curso de Cromatografía de Gases - Parque Científico de Madrid

CURSO DE CROMATOGRAFÍA DE GASES

Unidad de Biotransformaciones Industriales - Parque Científico de Madrid

COORDINADOR: José Vicente Sinisterra Gago Lugar: Madrid Fecha: 12, 13 y 14 de octubre de 2009 Horario: 9:30 a 18:00 h.

PROGRAMA:

(PRIMER DIA) Aspectos generales de la cromatografía de gases I Aspectos generales de la cromatografía de gases II

(SEGUNDO DIA) Técnicas de CG/EM Validación de métodos analíticos en cromatografía de gases

(TERCER DIA) Aplicaciones de la CG a la industria I Aplicaciones de la CG a la industris II

PRÁCTICAS: - FUNDAMENTOS DEL TRABAJO EN CROMATOGRAFÍA. - VALIDACIÓN DE UN MÉTODO ANALÍTICO DE SEPARACIÓN CROMATOGRÁFICA. - APLICACIÓN A LA DETERMINACIÓN DE ISOMENTOL COMO IMPUREZA DEL MENTOL. - ANÁLISIS DE UN PROCESO BIOCATALIZADO. - REDUCCIÓN ESTEREOSELECTIVA DE CETONAS.

OBJETIVO: Introducción a las técnicas de cromatografía de gases.

Más información: http://www.fpcm.es

Madrid+D - Entrevista al Prof. Sinisterra

Nuestras instalaciones están a disposición de empresas, investigadores y hospitales.

José Vicente Sinisterra. Responsable de la Unidad de Biotransformaciones Industriales del Parque Científico de Madrid. 17/09/2009

¿Qué servicios presta la Unidad de Biotransformaciones Industriales del Parque Científico de Madrid y en qué áreas?

La Unidad de Biotransformaciones Industriales del Parque Científico de Madrid aporta servicios de apoyo a la I+D+i, siguiendo normas ISO 9000, a empresas, grupos de investigación y hospitales, de diversos subsectores biotecnológicos, químicos o farmacéuticos. En este sentido, la Unidad dispone tanto de un equipo científico altamente cualificado, como de equipamiento e infraestructuras de última generación para la realización de distintos servicios científicos.

La labor de apoyo a empresas que desarrolla la Unidad no se circunscribe a un área de conocimiento concreto, ya que este concepto, de indudable utilidad docente, está desfasado desde la perspectiva actual de la I+D+i. Nuestra labor abarca distintas áreas de trabajo como la biotecnología (que no posee un área de conocimiento específica a diferencia de Europa o EEUU), la química orgánica, la microbiología industrial, la química farmacéutica, la química analítica o la tecnología farmacéutica. Todas ellas intervienen en las distintas industrias con las que colaboramos: alimentaria, farmacéutica, cosmética, etc.

¿Desde cuándo es Responsable de la Unidad de Biotransformaciones Industriales del PCM?

Soy responsable de la Unidad desde su creación en 2006, por acuerdo entre la Universidad Complutense de Madrid (UCM) y el Parque Científico de Madrid (PCM). En la UCM ejerzo como catedrático de la Facultad de Farmacia y en la actualidad comparto mi dedicación docente e investigadora en la Universidad con mi labor como responsable de una de las plataformas tecnológicas del Parque.

¿Qué valor añadido aportan los servicios de la Unidad a la comunidad investigadora y productiva del sector farmacéutico?

Un servicio de calidad a las empresas no se puede prestar sin una investigación actualizada y un conocimiento de las últimas innovaciones que van surgiendo. Esto se aplica a cualquier área de conocimiento. Es precisamente por eso, por lo que desde la Unidad de Biotransformaciones del PCM siempre hemos procurado la colaboración con el Grupo de Investigación en Biotransformaciones BTG que cuenta con investigadores de la UCM, la Universidad Autónoma (UAM) y el Consejo Superior de Investigaciones Científicas (CSIC). Este grupo tiene investigadores de prestigio europeo en biotecnología, química orgánica y desarrollo farmacéutico.

Por otro lado, la Unidad de Biotransformaciones se compone de personal altamente cualificado: dos técnicos Torres Quevedo y un técnico del PCM. Todos ellos prestan una dedicación al 100% a la Unidad. Además, contamos con tres becarios de investigación del BTG, que también colaboran en trabajos de la Unidad para empresas y OPIs, y con estudiantes, a través de convenios de intercambio como el que mantiene el PCM con el Instituto de Comercio Exterior de Portugal (ICEP), y procedentes de Masteres en Biotecnología de la UAM.

¿Cuáles son los servicios científicos más innovadores que ofrece la Unidad de Biotransformaciones Industriales y de qué forma redundan en los productos o servicios que se comercializan en la actualidad?

Los servicios que ofrecemos son muy diversos y se engloban en dos categorías: análisis y control de calidad; y apoyo alas empresas en I+D+i.

Realizamos análisis y control de calidad según la normativa vigente de farmacopea. Este trabajo es necesario para que una empresa pueda presentar sus productos en el mercado con una garantía de fiabilidad. Es un requisito indispensable en las industrias farmacéutica, cosmética y alimentaria, biotecnológica y de química fina.

También se prestan servicios de microbiología industrial trabajando con microorganismos procariotas para la producción de enzimas o de metabolitos de interés.

¿Cuáles son los retos inmediatos de la Unidad de Biotransformaciones Industriales?

El reto fundamental de la Unidad de Biotransformaciones es la creación de un laboratorio dotado de normas GLP (Good Laboratory Practice) y la implantación de un servicio de calidad homologable por la Agencia Española del Medicamento y Productos Sanitarios que abra al PCM un nuevo campo de trabajo de apoyo tanto a las empresas incubadas en el PCM, como al resto de empresas y de potenciales usuarios de estos servicios.

Por otro lado, desde la Unidad también se imparten cursos teórico-prácticos, en el marco del programa de formación del Parque Científico de Madrid, sobre cromatografía líquida y su aplicación a laboratorios industriales de control de calidad, de cromatografía de gases y de formación de postgrado en tecnología farmacéutica.

¿Qué tipo de usuario utiliza los servicios de la Unidad?

Prestamos servicios a un amplio espectro de usuarios, en su mayoría empresas privadas externas al PCM, tales como: Abbott, S.A., Cantabria Pharma, LETI…; seguido de empresas incubadas en el propio Parque Científico de Madrid, como Apoteknos; así como a grupos de investigación de las universidades Complutense y Autónoma y del CSIC.

¿Qué ventajas supone la Unidad de Biotransformaciones Industriales para las empresas biotecnológicas incubadas en el PCM?

Las ventajas son numerosas. Las empresas asociadas en el Parque Científico de Madrid, y en este caso concreto las biotecnológicas, pueden acceder a un servicio necesario para desarrollar su actividad a un coste muy asequible. El servicio prestado les permite presentar dossieres en agencias de control de calidad de producción españolas o europeas, al seguirse la normativa de la Farmacopea y de la ASTM (Association of Standard and Testing Materials)en los ensayos que se realizan. Esta política, aplicable también para el resto de plataformas tecnológicas que ofrece el PCM, permite a la comunidad emprendedora disponer de todas las infraestructuras científicas para lograr el éxito de sus proyectos empresariales. La Unidad de Biotransformaciones del PCM tiene a su disposición el asesoramiento del BTG, homologado por la Comunidad de Madrid, pudiendo acceder también a los servicios científicos de esta última, lo que le sitúa en un referente consolidado y de prestigio para los usuarios.

La colaboración con el BTG,de reconocido prestigio europeo en el campo de la Biotecnología, y la presencia en el edificio del PCM en Tres Cantos, donde además se encuentra la Bioincubadora del PCM, que en la actualidad aloja a 36 empresas innovadoras, supone un entorno privilegiado para que los proyectos de empresa que están empezando se desarrollen adecuadamente.

En su opinión ¿En qué medida son innovadores los servicios que se ofrecen desde la Unidad de Biotransformaciones Industriales del Parque Científico de Madrid?

La Unidad, mediante su colaboración con el BTG, supone una herramienta de valor añadido tanto para las empresas asociadas, como para otras empresas y grupos de investigación del sector. La función de los Parques Científicos es precisamente esa, ofrecer todo un sistema de apoyo encaminado a fortalecer la I+D+i.

Nuestra función como entidad se enmarca a su vez dentro de la denominada tercera misión de la Universidad y en su proceso de modernización. Instalaciones científicas costosas, como las que tenemos en la Unidad, se ponen a disposición de la comunidad investigadora, empresas y hospitales, y esa interacción es, en definitiva, la que fortalece nuestra misión en la sociedad, procurando que los avances científico-tecnológicos se concreten en servicios y productos para uso de los ciudadanos.

http://www.madrimasd.org/cienciaysociedad/entrevistas/revista-madrimasd/detalleEmpresa.asp?id=222

Curso de Cromatografía HPLC

COORDINADOR: José Vicente Sinisterra Gago
Lugar: Madrid Fecha: 28, 29 Y 30 de septiembre y 1, 2 de octubre de 2009
Horario: 9:30 a 18:00 h.

PROGRAMA:

(PRIMER DIA) Fundamentos de la técnica de cromatografía HPLC I Fundamentos de la técnica de cromatografía HPLC II

(SEGUNDO DIA) Conceptos básicos sobre las fases móviles en HPLC Nuevos desarrollos de HPLC

(TERCER DIA) Tipos de detectores en HPLC La técnica HPLC/EM

(CUARTO DIA) Validación en métodos en HPLC I Validación en métodos HPLC II

(QUINTO DIA)
Aplicaciones de la técnica a la investigación Aplicaciones de la técnica a la industria

PRÁCTICAS: - VALIDACIÓN DE MÉTODOS ANALÍTICOS Y VERIFICACIÓN DE LA ADECUACIÓN DEL SISTEMA DE UN ANÁLISIS CROMATOGRÁFICO. - PAUTAS A SEGUIR EN LA CALIFICACIÓN DE UN EQUIPO HPLC. - APLICACIONES DE LOS DETECTORES DE DICROÍSMO CIRCULARQ (DC) Y EVAPORATIVE LIGHT SCATTERING (ELSD). - ANÁLISIS DE SULFAMIDAS POR LC-MS.

OBJETIVO: Introducción a las técnicas de HPLC y su aplicación a laboratorios industriales de control de calidad.
Más información: www.fpcm.es

Biotrans 2009 - Bern, Switzerland

A work presented by the Biotransformations Group received the prize to the best poster of the Congress. In the image, Prof. José María Sánchez Montero receives the prize at the end of the Meeting. http://www,biotrans2009.org/

Biotrans takes place every two years in Europe with attendance of 500-600 participants from academia and industry, focusing on applied and fundamental aspects of biocatalysis. Biotrans 2009 will take place from July 5 - 9 in Berne, capital city of Switzerland, located in a beautiful setting at the foot of the Alps (http://www.berninfo.com/en/welcome.cfm). Topics: Biotransformations in organic synthesis, Industrial processes & development, Metabolic engineering, Directed evolution & screening, Bioinformatics, protein structure, modeling & mechanisms, Carbohydrate active enzymes Former Biotrans Meetings: Oviedo (ES) 2007 ; Delft (NL) 2005 ; Olomouc (CZ) 2003 ; Darmstadt (D) 2001 ; Taormina Naxos (I) 1999; La Grande Motte (F) 1997; Warwick (UK) 1995: Graz (A) 1993

New Photos to the Biotransformations Group album

Entrevista - Ibercampus

Unidad de Biotransformaciones del PCM

José Vicente Sinisterra: "Un servicio de calidad a las empresas no se puede prestar si no se investiga y no se está al día de las innovaciones"

José Vicente Sinisterra es responsable de la Unidad de Biotransformaciones Industriales del Parque Científico de Madrid desde su creación en 2006. Sinisterra nos acerca en esta entrevista al funcionamiento de esta herramienta que se acopla a la perfección a la filosofía de todo parque científico "ofrecer todo un sistema de apoyo encaminado a fortalecer la I+D+i".
ibercampus.es

P.- ¿Desde cuándo es Responsable de la Unidad de Biotransformaciones Industriales del PCM?
R.- Soy responsable de la Unidad de Biotransformaciones desde su creación en 2006 por acuerdo entre la Universidad Complutense de Madrid y el Parque Científico de Madrid.
P.- ¿Cuál es la vinculación a la Universidad Complutense de Madrid?
R.- Soy catedrático de la Facultad de Farmacia de la UCM y comparto mi dedicación docente e investigadora en la UCM con mi labor como responsable de la Unidad de Biotransformaciones del PCM.
Un servicio de calidad a las empresas no se puede prestar si no se investiga y no se está al día de las innovaciones que van surgiendo, por ello siempre he pretendido que la Unidad de Biotransformaciones Industriales del Parque cuente con el apoyo y colaboración del Grupo de investigación de calidad de la UCM/CM – Grupo de Biotransformaciones (BTG) – donde hay investigadores de la UCM, UAM y CSIC. Este grupo de investigación tiene investigadores de prestigio europeo en los campos de biotecnología, química orgánica y desarrollo farmacéutico. Asimismo hay que indicar que parte del equipamiento científico de la Unidad ha sido adquirido por el Grupo de Investigación de Biotransformaciones Industriales utilizándose tanto para la investigación como para los servicios de apoyo a las empresas.
P.- ¿De qué personal dispone la Unidad?
R.- La Unidad de Biotransformaciones se compone de dos técnicos Torres Quevedo y un técnico contratado del PCM. Todos ellos prestan una dedicación al 100% a la Unidad. Asimismo contamos con la colaboración de tres becarios de investigación de BTG, que también colaboran en trabajos de la Unidad para empresas y OPIs. Asimismo, contamos en la Unidad con la colaboración de estudiantes, a través de convenios de intercambio como el que mantiene el PCM con el ICEP de Portugal, y procedentes de Másteres en Biotecnología de la UAM.
P.- ¿Con qué áreas de conocimientos relacionan los servicios que presta la Unidad de Biotransformaciones Industriales?
R.- La labor de apoyo a empresas que desarrolla la Unidad de Biotransformaciones Industriales no se circunscribe a un área de conocimiento concreto, ya que este concepto, de indudable utilidad docente, esta desfasado desde el punto de vista de la actual I+D+i. Nuestra labor abarca distintas áreas de trabajo como la Biotecnología (que no posee un área de conocimiento específica a diferencia de Europa o USA), la Química Orgánica, la Microbiología industrial, la Química Farmacéutica, Química Analítica o la Tecnología Farmacéutica. Todas ellas intervienen en las distintas industrias con las que colaboramos: alimentaria, farmacéutica, cosmética, etc.
P.- ¿Qué valor añadido aportan los servicios de la Unidad de Biotransformaciones a la comunidad investigadora y productiva del sector farmacéutico?
R.- La tarea de la Unidad de Biotransformaciones Industriales del PCM es aportar servicios de apoyo a la I+D+i siguiendo normas ISO 9000, tanto a empresas, grupos de investigación y hospitales, de todas las áreas mencionadas anteriormente. En este sentido, la Unidad de Biotransformaciones dispone, tanto de un equipo científico altamente cualificado, así como un equipamiento e infraestructuras de última generación para la realización de distintos servicios científicos.
P.- ¿Cuáles son los servicios científicos más innovadores que ofrece la Unidad de Biotransformaciones y de qué forma redundan en los productos o servicios que se comercializan en la actualidad?
R.- Los servicios que ofrecemos son muy diversos y se engloban en dos categorías: análisis y control de calidad, por un lado, y apoyo a las empresas en I+D+i, por otro.
Realizamos análisis y control de calidad según la normativa vigente de farmacopea. Este trabajo es necesario para que una empresa pueda presentar sus productos en el mercado con una garantía de fiabilidad. Es un requisito indispensable en las industrias farmacéutica, cosmética y alimentaría, biotecnológica y de química fina.
También se prestan servicios de microbiología industrial trabajando con microorganismos procariotas para la producción de enzimas o de metabolitos de interés.
P.- ¿Cuáles son los retos inmediatos de la Unidad de Biotransformaciones Industriales?
R.- El reto fundamental de la Unidad de Biotransformaciones es la creación de un laboratorio dotado de normas GLP y la implantación de un servicio de calidad homologable por la Agencia Española del Medicamento y Productos Sanitarios que abra al PCM un nuevo campo de trabajo de apoyo tanto a las empresas incubadas en el PCM, como al resto de empresas y de potenciales usuarios de estos servicios.
Por otro lado, desde la Unidad también se imparten cursos teórico-prácticos, en el marco del programa de formación del Parque Científico de Madrid, sobre cromatografía líquida y su aplicación a laboratorios industriales de control de calidad, de cromatografía de gases y de formación de postgrado en tecnología farmacéutica.
P.- ¿Qué tipo de usuario utiliza los servicios de la Unidad de Biotransformaciones?
R.- Prestamos servicios a un amplio espectro de usuarios, siendo en su mayoría empresas privadas externas al PCM, tales como: Abbott S.A., Cantabria Pharma, LETI,…, seguido de empresas incubadas en el propio Parque Científico de Madrid, como Apoteknos, así como a grupos de investigación de las universidades Complutense, Autónoma y del CSIC.
P.- ¿Qué ventajas supone la Unidad de Biotransformaciones para las empresas biotecnológicas incubadas en el PCM?
R.- Las ventajas son numerosas. Las empresas asociadas en el Parque Científico de Madrid, y en este caso concreto las biotecnológicas, pueden acceder a un servicio necesario para desarrollar su actividad a un coste muy asequible. El servicio prestado les permite poder presentar dossieres en Agencias de control de calidad de producción españolas o europeas, al seguirse la normativa de la Farmacopea y ASTM en los ensayos que se realizan. Esta política, aplicable también para el resto de plataformas tecnológicas que ofrece el PCM, permite a la comunidad emprendedora disponer de todas las infraestructuras científicas para lograr el éxito de sus proyectos empresariales. La Unidad de Biotransformaciones del PCM tiene a su disposición el asesoramiento del Grupo de Investigación de la Universidad Complutense de Madrid, homologado por la Comunidad de Madrid, pudiendo acceder también a los servicios científicos de esta última, lo que le sitúa en un referente consolidado y de prestigio para los usuarios.
La colaboración con el BTG, de reconocido prestigio europeo en el campo de la Biotecnología, y la presencia en el edificio del PCM en Tres Cantos, donde además se encuentra la Bioincubadora del PCM, que en la actualidad aloja a 36 empresas innovadoras, supone un entorno privilegiado para que los proyectos de empresa que están empezando se desarrollen adecuadamente.
P.- ¿Qué aporta la Unidad de Biotransformaciones Industriales a la I+D+i?
R.- La Unidad de Biotransformaciones Industriales, mediante su colaboración con el BTG, supone una herramienta de valor añadido tanto para las empresas asociadas, como para otras empresas y grupos de investigación. La función de los Parques Científicos es precisamente esa, ofrecer todo un sistema de apoyo encaminado a fortalecer la I+D+i.
El papel de la Unidad de Biotransformaciones se refuerza además con la presencia en congresos internacionales donde los miembros científicos del grupo han sido conferenciantes invitados. Así, recientemente la Unidad ha presentado tres trabajos en el Congreso Biotrans-09 celebrado en Berna en Julio 2009, que se han realizado parcialmente en la Unidad de Biotransformaciones y una comunicación oral en el Congreso Europeo de Carbohidratos, celebrado en Viena en Julio 2009.
La unidad figura en los trabajos que realizan parcialmente en la misma. Entre ellos podemos citar como más significativos de 2009, los siguientes:
CARBALLEIRA J.D., FERNANDEZ-LUCAS J., QUEZADA M.A., HERNAIZ M.J., ALCANTARA A.R., SIMEO Y, SINISTERRA J.V. Industrial Biotransformations. Encyclopedia of Microbiology.
Schaechter M. ed. Elsevier, :Oxford (UK). 212-251 (2009)
ALMENDROS M., SINISTERRA J.V., BERENGUER J. Thermus thermophilus strains active in purine nucleoside synthesis. Molecules 14, 1279-1287(2009)
SIMEO Y, SINISTERRA J.V. Biotransformation of terpenoids: A green alternative for producing molecules with pharmacological activity Mini-Reviews in Organic Chemistry 6(2), 128-134 (2009)
SIMEO Y, SINISTERRA J.V.,ALCANTARA A.R. Regioselective enzymatic acylation of pharmacologically interesting nucleosides in 2-methyltetrahydrofuran, a greener substitute of THF. Geren Chemistry 11, 855-862 (2009).
Por último mencionar que este mes de septiembre se va a presentar en la UCM una tesis doctoral realizada por un becario mexicano del BTG, elaborada parcialmente en la Unidad.
Fuente: Parque Científico de Madrid

Regioselective enzymatic acylation of pharmacologically interesting nucleosides in 2-methyltetrahydrofuran, a greener substitute for THF

Green Chem., 2009, 11, 855 - 862, http://dx.doi.org/10.1039/b818992g
Regioselective enzymatic acylation of pharmacologically interesting nucleosides in 2-methyltetrahydrofuran, a greener substitute for THF
Yolanda Simeó, José Vicente Sinisterra and Andrés R. Alcántara
1--Arabinofuranosyl uracil, 9--arabinofuranosyl adenosine, 2-O-(2-methoxyethyl)-5-methyl uridine, adenosine and uridine were enzymatically acylated with hexanoic anhydride and vinyl esters by CALB lipase (lipase B from Candida antarctica) with excellent regioselectivity in many cases and analytical reaction yields above 90%. The influence of the stereochemistry of the hydroxyl group on C-2 was studied. Some of these esterifications were carried out in 2-methyltetrahydrofuran (MeTHF), which is described as an excellent substitute for THF in biocatalysed processes in organic media. This application for this green solvent is a proof-of-concept opening the use of MeTHF in biotransformations.

Microbial cells as catalysts for stereoselective red-ox reactions - Biotechnology Advances 2009

J.D. Carballeira, M.A. Quezada, P. Hoyos, Y. Simeó, M.J. Hernaiz, A.R. Alcantara and J.V. Sinisterra.
- Industrial Biotransformations Service, Scientific Park of Madrid, C/ Santiago Grisolía n° 2, Tres Cantos, 28760 Madrid, Spain
- Molecular Interactions Service, Scientific Park of Madrid, Faculty of Pharmacy, Universidad Complutense, 28040 Madrid, Spain
- Biotransformations Group, Department of Organic & Pharmaceutical Chemistry, Faculty of Pharmacy, Universidad Complutense, 28040 Madrid, Spain

Enzyme catalyzed reactions are commonly used at laboratory or industrial scale. Contrarily, the whole cells catalyzed reactions are restricted to special cases. The tremendous advances in the last years in Molecular Biology and more specifically in Metabolic Engineering and Directed Enzyme Evolution have opened the door to create tailor-made microorganisms or “designer bugs” for industrial purposes. Whole cells catalysts can be much more readily and inexpensively prepared than purified enzymes and the enzymes - inside the cells – are protected from the external environment and stabilized by the intracellular medium. Three situations have traditionally been considered convenient to select the use of whole cell catalyzed processes against the free enzyme catalyzed process: i) when the enzyme is intracellular; ii) when the enzyme needs a cofactor to carry out the catalytic act and iii) in the development of multi-enzymatic processes. Redox reactions represent the molecular basis for energy generation in the cell. These reactions are catalyzed by intracellular enzymes and are cofactor dependent as redox reactions need electron carriers as helpers in reduction reactions (gain of electrons) or oxidation (loss of electrons).
In this review we present an overview of the state of the art of red-ox biotransformations catalyzed by whole cells - wild-type or genetically engineered microorganisms. Stereoselective reductions, hydroxylations of arenes and unfunctionalized alkanes, alkene monooxygenation, Baeyer-Villiger reactions are among the processes described along the text, focusing in their chemo-, regio- and stereoselectivity.
Keywords: Biotransformations; Biocatalysis; Whole-cell-catalysts; Cell-factories; Designer-bugs Immobilization of cells; stereoselective reactions; red-ox reactions

http://dx.doi.org/10.1016/j.biotechadv.2009.05.001

Efficient Horner-Wadsworth-Emmons intramolecular cyclisation of a N-substituted phthalimide promoted by KF-Alumina: a general tool for the synthesis o

Vittorio Pace, Fernando Martınez, Clara I. Nova, Marıa Fernández, José Vicente Sinisterra and Andrés R. Alcántara

Department of Organic and Pharmaceutical Chemistry, Pharmacy Faculty, Complutense University, Pza. Ramón y Cajal s/n, 28040 Madrid Spain

Industrial Biotransformations Service (SBI), Scientific Park of Madrid (PTM), C/ Santiago Grisolia 2, 28760 Tres Cantos, Madrid Spain

Abstract
An intramolecular Horner-Wadsworth-Emmons reaction promoted by KF-Alumina involving a N-substituted phthalimide, cleanly and efficiently furnishes an interesting α,β-unsaturated tricyclic enone which may undergo selective alkylations at the α’-position.

http://dx.doi.org/10.1016/j.tetlet.2009.04.029

Growth hormone improves lipoprotein concentration and arylesterase activity in mice with an atherogenic lipid profile induced by lactalbumin

E. LOPEZ-OLIVA, M. NUS, A. AGIS-TORRES, W. VILLARO, J.M. SANCHEZ-MONTERO, E. MUÑOZ-MARTINEZ, F.J. SANCHEZ-MUÑIZ

Sección Departamental de Fisiología Animal, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

Departamento de Nutrición y Bromatología I (Nutrición), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

Biotransformations Group, Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

The effect of growth hormone (GH) on arylesterase (AE), one of the activities of paraoxonase, has never been studied. The aims of the present study in mice were: (a) to compare the effect of age and sex on serum lipid and lipoprotein levels after consumption of lactalbumin- v. chow-based diets and (b) to study the effect of GH administration, age and sex on serum AE activity, lipid and lipoprotein and body fat levels in mice fed a lactalbumin diet. Seventy-two mice were divided into three age- and sex-matched experimental groups: (1) control chow (CC), (2) non-GH lactalbumin (NGL) and (3) GH-treated lactalbumin (GL) mice. Lactalbumin increased total cholesterol, (LDL+VLDL)-cholesterol and TAG and diminished HDL-cholesterol in all animals

http://dx.doi.org/10.1017/S0007114508025014

A global benchmark study using affinity-based biosensors

Prof. MJ Hernaiz is one of the co-authors of this global study

To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
Keywords: Biacore; Kinetics; Optical biosensor; Surface plasmon resonance

http://dx.doi.org/10.1016/j.ab.2008.11.021

Glycan Tagging to Produce Bioactive Ligands for a Surface Plasmon Resonance (SPR) Study via Immobilization on Different Surfaces.

F.J MUÑOZ, J. PEREZ, A. RUMBERO, J.I. SANTOS, F.J. CAÑADA, S. ANDRE, H.J. GABIUS, J. JIMENEZ-BARBAERO, J.V. SINISTERRA, M.J. HERNAIZ.

Departamento de Quimica Organica y Farmaceutica, Universidad Complutense de Madrid, Plaza Ramon y Cajal s/n. 28040 Madrid, Spain
Departamento de Quimica Organica, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain

Departamento de Ciencia de Proteinas, CIB-CSIC, c/Ramiro de Maeztu 9, 28040 Madrid, Spain, Institut fur Physiologische Chemie, Tierarztliche Fakultat, Ludwig-Maximilians-Universitat, Munchen, Veterinarstr 13, 80539 Munchen, Germany

Servicio de Biotransformaciones Industriales, Parque Cientifico de Madrid C/Santiago Grisolia, 28760 Tres Cantos, Spain & Servicio de Interacciones Biomoleculares, Parque Cientifico de Madrid, Pz/Ramon y Cajal s/n. 28040 Madrid, Spain.

Suitable glycan derivatives will find immediate application in the study of their interactions. Here, we present an efficient synthetic strategy to introduce a fluorescent tag functionalized with an amino group into a model disaccharide structure (lactose). This strategy led to the maintenance of bioactivity, checked by the study of the interaction of this bioconjugate with a plant lectin (mistletoe lectin 1) by NMR spectroscopy, computational docking, and surface plasmon resonance (SPR). To demonstrate the versatility of this approach, we immobilized the new glycan derivatives on different surfaces, and a comparative analysis is presented and can be successfully used for biomimetic carbohydrate-protein interaction studies on the SPR biochip.

http://dx.doi.org/10.1021/bc800350q

Biotransformations. vol. 1, pp. 212-251. Encyclopedia of Microbiology 3rd Edition. Oxford. Elsevier

J.D. CARBALLEIRA, J. FERNANDEZ-LUCAS, M.A. QUEZADA, M.J. HERNAIZ, A.R. ALCANTARA, Y. SIMEO, J.V. SINISTERRA

The application of whole-cell-catalyzed biotransformations is an emerging field that opens up a myriad of new possibilities for the industrial application of biocatalysts. In this article, the new technologies to design tailor-made cells for specific reactions as well as some interesting applied processes catalyzed by intracellular enzymes are presented.

Encyclopedia of Microbiology
Moselio Schaechter, San Diego State University, CA, USA
Six-Volume Set, 1-6 Hardbound, 4600 pages, publication date: APR-2009
ISBN-13: 978-0-12-373939-1
ISBN-10: 0-12-373939-X
Imprint: ACADEMIC PRESS

Monascus kaoliang CBS 302.78 immobilized in polyurethane foam using iso-propanol as co-substrate: Optimized immobilization conditions of a fungus as b

M.A. Quezada, J.D. Carballeira and J.V. Sinisterra

Department of Chemistry, Faculty of Chemical Engineering, University of Trujillo, Peru
Industrial Biotransformations Service, Scientific Park of Madrid, C/Santiago Grisolia No. 2, Parque Tecnológico de Madrid, 28760 Tres Cantos, Madrid, Spain

Biotransformations Group, Organic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Universidad Complutense, 28040 Madrid, Spain

Abstract
Monascus kaoliang was selected after a microbial screening as a highly active and selective whole cell catalyst for the reduction of ketones. In the present paper we describe the optimum growing conditions and an interesting immobilization procedure by adsorption in polyurethane foams (PUFs). This methodology is easy to perform and the immobilized catalyst is active, stable and reusable. The use of different co-substrates for cofactor regeneration was also tested and iso-propanol (i-PrOH) was found as the best co-substrate, as it leads to a catalyst reusable for 17 cycles, displaying better NADH regeneration properties than others e.g., glucose (10 cycles) or saccharose (6 cycles). The reduction of different prochiral ketones showed that the ketone reductase activity of this mould follows the Prelog’s rule and kinetic experiments demonstrated that the process follows a pseudo-first kinetic order.

Biotransformation of Terpenoids: A Green Alternative for Producing Molecules with Pharmacological Activity

Y. Simeó and J.V. Sinisterra

Mini Reviews in Organic Chemistry 2009

Terpenoids are natural products of great interest due to their broad application scope. They are employed as agrochemicals, drugs, fragrances, flavours and pigments. In the search of new derivatives with improved properties, the use of biocatalysts is being constantly increased, especially in redox processes. They can give rise to stereo- and regioselective products and/or compounds functionalized in remote positions difficult to reach by means of traditional organic chemistry. In this review, the application of whole cell catalyzed biotransformations of terpenoids to obtain new drug targets or to increase the pharmacological activity is presented.

http://www.bentham.org/mroc/

Defining the Epitope Region of a Peptide from the Streptomyces coelicolor Phosphoenolpyruvate:Sugar Phosphotransferase System Able to Bind to the Enzy

E. HURTADO-GOMEZ, O. ABIAN, F. J. MUÑOZ , M.J. HERNAIZ, A. VELAZQUEZ-CAMPOY, J.L. NEIRA

Abstract
The bacterial PEP:sugar PTS consists of a cascade of several proteins involved in the uptake and phosphorylation of carbohydrates, and in signal transduction pathways. Its uniqueness in bacteria makes the PTS a target for new antibacterial drugs. These drugs can be obtained from peptides or protein fragments able to interfere with the first reaction of the protein cascade: the phosphorylation of the HPr by the first enzyme, the so-called enzyme EI. To that end, we designed a peptide, HPr9–30, spanning residues 9 to 30 of the intact HPr protein, containing the active site histidine (His-15) and the first α-helix of HPr of Streptomyces coelicolor, HPrsc. By using fluorescence and circular dichroism, we first determined qualitatively that HPrsc and HPr9–30 did bind to EIsc, the enzyme EI from S. coelicolor. Then, we determined quantitatively the binding affinities of HPr9–30 and HPrsc for EIsc by using ITC and STD-NMR. The STD-NMR experiments indicate that the epitope region of HPr9–30 was formed by residues Leu-14, His-15, Ile-21, and Val-23. The binding reaction between EIsc and HPrsc is enthalpy driven and in other species is entropy driven; further, the affinity of HPrsc for EIsc was smaller than in other species. However, the affinity of HPr9–30 for EIsc was only moderately lower than that of EIsc for HPrsc, suggesting that this peptide could be considered a promising hit compound for designing new inhibitors against the PTS.
Abbreviations: PEP, phosphoenolpyruvate; CD, circular dichroism; EIsc, enzyme I of Streptomyces coelicolor; EIec, enzyme I of E. coli; HPrec, histidine phosphocarrier protein of Escherichia coli; HPrsc, histidine phosphocarrier protein of Streptomyces coelicolor; HPr9-30, peptide comprising residues Gly-9 to Gly-30 of the intact HPrsc; ITC, isothermal titration calorimetry; NMR, nuclear magnetic resonance; PTS, sugar phosphotransferase system; STD, saturation transfer difference; TFE, trifluoroethanol; TSP, sodium trimethylsilyl [2,2,3,3-2H4] propionate; UV, ultraviolet

http://dx.doi.org/10.1529/biophysj.107.126664

Versatile strategy for the synthesis of biotin-labelled glycans, their immobilization to establish a bioactive surface and interaction studies with a

F.J MUÑOZ, A. RUMBERO, J.V. SINISTERRA, J.I. SANTOS, S. ANDRE, H.J. GABIUS, J. JIMENEZ-BARBERO, M.J. HERNAIZ

Abstract The emerging role of glycans as versatile biochemical signals in diverse aspects of cellular sociology calls for establishment of sensitive methods to monitor carbohydrate recognition by receptors such as lectins. Most of these techniques involve the immobilization of one of the binding partners on a surface, e.g. atomic force microscopy, glycan array and Surface Plasmon Resonance (SPR), hereby simulating cell surface presentation. Here, we report the synthesis of fluorescent glycoconjugates, with a functionalization strategy which avoids the frequently occurring ring opening at the reducing end for further immobilization on a surface or derivatization with biotin. In order to improve the versatility of these derivatized glycans for biological studies, a new approach for the synthesis of biotinylated and fluorescent glycans has also been realized. Finally, to illustrate their usefulness the neoglycoconjugates were immobilized on different surfaces, and the interaction analysis with a model lectin, the toxin from mistletoe, proved them to act as potent ligands, underscoring the merit of the presented synthetic approach.
Electronic supplementary material The online version of this article (doi:10.1007/s10719-008-9115-y) contains supplementary material, which is available to authorized users.

http://dx.doi.org/10.1007/s10719-008-9115-y

Esterification reactions catalyzed by lipases immobilized in organogels: effect of temperature and substrate diffusion

M. ZOUMPANIOTI, P. PARMAKLIS, P. DOMINGUEZ DE MARIA, H. STAMATIS, J.V. SINISTERRA, A. XENAKIS

Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece

Biotransformations Group, Faculty of Pharmacy, Universidad Complutense, Madrid, Spain

Biological Applications and Technologies Department, University of Ioannina, Ioannina, Greece

Abstract

Rhizomucor miehei lipase was immobilized in hydroxy(propylmethyl) cellulose or agar gels containing lecithin or AOT microemulsions. The effect of the diffusion of substrates and products to this catalyst was studied, as well as the effect of temperature on the initial rate of ester synthesis. The composition of the gel affects the reaction rate due to mass transport phenomena. The apparent activation energies were higher for the systems based on agar, independently of the microemulsion used, and lower for the systems based on AOT microemulsions, independently of the polymer used.

http://dx.doi.org/10.1007/s10529-008-9734-1