Symposium with UNICAT cluster of excellence from Berlin

UNICAT (Unifying concepts in Catalysis) is a Cluster of Excellence that gathers about 240 staff members of 4 universities and 2 Max Planck research institutes of Berlin and Potsdam around the economically important field of catalysis. More information on UNICAT here.
The scientific day will be take place in the Saint-Jérôme campus of the Aix Marseille University. Several scientists from the UNICAT cluster of excellence in Berlin (Unifying concepts in Catalysis) will be welcomed. 


Program


8:45-9:00 Introduction words
Prof. Jean Marc Pons, Dean of Science Faculty of Aix Marseille Université
Prof. Matthias Driess, chair of UNICAT cluster of excellence

1st session. Chair: Silviu Balaban
9:00-9:25 Bruno Guigliarelli "The Molybdo-enzyme challenges: from reactivity to biogenesis"
9:25-9:50 Peter Hildebrandt "Vibrational spectroscopic approaches for elucidating the mechanisms of enzymatic processes"
9:50-10:15 Frédéric Fagès "Sub-picosecond to nanosecond excited-state dynamics in T-shaped curcuminoids"

Coffee

2nd session. Chair: Dr. Ling Peng
10:45-11h10 Holger Dobbek: "CO and CO2 activation at enzymatic Ni,Fe-clusters"
11:10-11h35 Thierry Tron "New bio-catalysts based on functionnalized laccases"
11:35-12:00 Silke Leimkuelher "Mechanism of CO2 caption and release by enzymatic systems"
12:00-12:25 Axel Magalon "Sulfuration of the MO center of formate dehydrogenases is essential for conversion of formate to CO2"

Lunch (buffet, salle des actes)

3rd session. Chair: Elizabeth Lojou
14:00-14:25 Oliver Lenz "Biocatalytic H2 conversion in the presence of O2".
14:25-14:50 Christophe Léger "Investigations of the mechanism of FeFe hydrogenases: catalysis and inhibition."
14:50-15:15 Ulla Wollenberger "Bioelectrocatalytic reactions of Molybdo- a. and heme proteins and biosensor application"
15:15-15:40 Olga Iranzo "Fine-tuning the Structure of His-containing Peptides for Copper Binding"

coffee

4th session. Chair: Marius Réglier
16:10-16:35 Christian Limberg "Biomimetic complexes modeling non-heme iron dioxygenases"
16:35-17:00 Jalila Simaan "Mechanistic investigation of a non-heme iron(II) containing enzyme: ACC Oxidase"
17:00-17:25 Matthias Driess "Bioinspired Inorganic Synthesis: Progress in Artificial Water Oxidation and Oxygen Reduction Catalysis"
17:25-17:50 Cyril Bressy "How Small Organic Molecules could act as Mimic of Enzyme? Studies in Enantioselective Organocatalytic Acyl Transfer" 

Concluding remarks


The conference day will take place at "Saint Jérôme" campus of Aix Marseille Université (Amphi EGIM SUD).

Registration is free. Please register before March 21rst

Titles and Abstracts:

1st session. Chair: Silviu Balaban

9:00-9:25 Bruno Guigliarelli
Bioénergétique et Ingéniérie des Protéines, CNRS / Aix Marseille Université, Marseille
"The Molybdo-enzyme challenges: from reactivity to biogenesis"

Molybdenum enzymes constitute a wide enzyme family found in nearly all organisms. In prokaryotes, these enzymes contain a mononuclear Mo-cofactor in which the Mo ion is coordinated by two pyranopterin guanosine dinucleotide (PGD) moieties and by an additional protein ligand. Despite the similarity of their Mo-bisPGD cofactor, these enzymes are very diverse in terms of structure and subunit composition and are able to use a broad diversity of substrates, being involved in the major biogeochemical cycle of carbon, nitrogen, sulfur and metalloids (1). However, in spite of numerous crystallographic and spectroscopic studies, the molecular factors which trigger their reactivity remains largely debated (2). By combining site-directed mutagenesis, EPR spectroscopy, electrochemistry and DFT calculations on model Mo-enzymes, we brought new insights on the activation process of these enzymes and on the role of the various spectroscopically detected Mo species in catalysis. The potential role of pyranopterin in these processes is clearly evidenced (3) which emphasizes the need of a clear understanding of biogenesis steps leading to active enzymes. Such information will be essential for the future design of artificial molybdo-enzymes with controlled reactivity.

[1] S. Grimaldi, B. Schoepp-Cothenet, P. Ceccaldi, B. Guigliarelli, A. Magalon, Biochim. Biophys. Acta (2013) 1827, 1048-85. [2] S. Metz, W. Thiel, Coord. Chem. Rev. (2011) 255, 1085-1103. [3] Jacques JG, Fourmond V, Arnoux P, Sabaty M, Etienne E, Grosse S, Biaso F, Bertrand P, Pignol D, Léger C, Guigliarelli B, Burlat B., Biochim Biophys Acta. (2014) 1837, 277-86.

9:25-9:50 Peter Hildebrandt
Technische Universität Berlin, Inst. f. Chemie / FG Biophysikalische Chemie, Berlin
"Vibrational spectroscopic approaches for elucidating the mechanisms of enzymatic processes"

Spectroscopic techniques, and among them specifically resonance Raman (RR) and IR spectroscopy, are indispensable tools for elucidating the mechanism of enzymes on a molecular basis. In this account, we will introduce modern RR and IR spectroscopic approaches that rely upon the interplay with other experimental and theoretical techniques. We will demonstrate the potential of these approaches on the basis of various examples of metalloenzymes such as hydrogenases, sulfite oxidase, or complex I. Special emphasis is laid on approaches (surface enhanced resonance Raman – SERR; surface enhanced infrared absorption – SEIRA) for studying (redox) enzymes immobilized on electrodes coated by membrane models. Finally, we will assess the potential of these techniques for in-situ investigations.

9:50-10:15 Frédéric FagèsCINaM UMR 7325, Marseille
"Sub-picosecond to nanosecond excited-state dynamics in T-shaped curcuminoids"

We report on the spectroscopic and photophysical behavior of T-shaped p-conjugated molecular structures based on a difluoroboron-containing curcuminoid unit linked to a tolane chromophore through the meso carbon atom of the dioxaborine ring. TD-DFT calculations show that optical transitions involve spatially disjointed molecular orbitals. Electronic absorption and fluorescence emission spectroscopies - steady-state and time-resolved – point to the occurrence of a complex manifold of excited states with intramolecular charge transfer character.

Coffee

2nd session. Chair: Dr. Ling Peng

10:45-11h10 Holger DobbekStrukturbiologie/Biochemie, Institut für Biologie, Humboldt-Universität zu Berlin
"CO and CO2 activation at enzymatic Ni,Fe-clusters"

Anoxic niches are providing habitats for microorganisms adapted to seemingly hostile environments. Carbon monoxide and carbon dioxide are used by diverse anaerobes as carbon and energy source. Different pathways of growth with CO/CO2 have been described under which the reductive acetyl-CoA pathway is likely primordial. Productive utilization of carbon dioxide is relying on the set of oxygen sensitive the metalloenzymes exploiting the metal organic chemistry of nickel and cobalt to synthesize acetyl-CoA from two molecules of CO2. In addition to the central catalysts, CO dehydrogenase and acetyl-CoA synthase, we recently started to investigate accessory proteins of the pathway exploiting ATP hydrolysis to drive electron transfer and metal incorporation to (re)activate the central players of the pathway. The talk will give an overview on the current status of our work and will focus on the strategy of CO / CO2 activation by the Ni,Fe-cluster of carbon monoxide dehydrogenates.

11:10-11h35 Thierry TronInstitut des Sciences Moléculaires de Marseille, Aix Marseille Université, CNRS, Marseille, France
"New bio-catalysts based on functionnalized laccases"

Laccases are very well known biocatalysts with great robustness, high oxidation power and substrate versatility (among other properties).[1] They contain a unique set of copper ions made of one each of the three types of biorelevant copper sites: type 1 (T1), type 2 (T2) and a binuclear type 3 (T3), and couple dioxygen reduction to the oxidation of substrates, either organic or metal ion.[2] They belong to the Blue Copper Binding Domain (BCBD) family of proteins in which the archetypal members are the plant or bacterial electron transfer protein cupredoxins (CUP). In this family, function is modulated by the number of CUP domains, the number and type copper atoms and the fusion to non metalled domains. Taking natural plasticity within the BCBD family as a source of inspiration for the engineering of laccases,[3, 4] we shape new catalysts based on a laccase functionnalized with different “plug-ins”.

One of our targets is a robust system where light absorption triggers electron transfer from a catalytic centre to a renewable electron acceptor. We have recently reported the light driven four-electron reduction of dioxygen to water via a laccase using either a [Ru(bpy)3]2+ or a [ZnTMPyP]4+ type chromophores and EDTA as sacrificial electron donor.[5] We present here the first example of photooxygenation of styrene with a system driven by an enzyme using dioxygen as a final and renewable electron acceptor. Substrate oxygenation occurs upon irradiation of the aerated enzyme solution containing a [Ru(bpy)3]2+ complex acting both as sensitizer and likely as a precursor of the catalytic species. Styrene oxygenation is dependent on the enzyme, dioxygen and light and is neither consecutive to a reaction with H2O2 nor with photo-generated O2 reactive species. The concomitant dioxygen reduction is dependent on styrene and light. Substantial amounts of styrene oxygenation products are obtained with this enzyme/sensitizer hybrid system thereby supporting its suitability for photo-driven transformations of substrates. Such a molecular photo-oxygenation catalyst using O2 as renewable electron acceptor allows avoiding the need of traditional systems for both a sacrificial electron acceptor and an overpressure of an inert gas.

[1] T. Tron, in Encyclopedia of Metalloproteins, Kret.singer, RH, Uversky, VN, Permyakov, EA. (Eds.) Springer, New York, 2013, pp. 1066-1070. [2] E. Solomon, U. Sundaram, T. Machonkin, Chem. Rev., 1996, 96, 2563-2605. [3] V. Balland, C. Hureau, A. Cusano, Y. Liu, T. Tron, B, Limoges, Chem. Eu. J., 2008, 14, 7186-92. [4] V. Robert, Y. Mekmouche, P. Rousselot Pailley, T. Tron, Curr. Genomics, 2011, 12, 123-129. [5] a) A. Simaan, Y. Mekmouche, C. Herrero, P. Moreno, A. Aukauloo, J. Delaire, M. Réglier, T. Tron. Chem. Eu. J., 2011, 17, 11743-11746; b) T. Lazarides, I. V. Sazanovich, A. J. Simaan, M. C. Kafentzi, M. Delor, Y. Mekmouche, B. Faure, M. Réglier, J. A. Weinstein, A. G. Coutsolelos, T. Tron, J. Am. Chem. Soc. 2013, 135, 3095-3103.

11:35-12:00 Silke Leimkuelher
Universität Potsdam, Institut für Biochemie und Biologie, Germany
"Mechanism of CO2 caption and release by enzymatic systems"

Formate dehydrogenase from Rhodobacter capsulatus (RcFDH) catalyzes the reversible conversion of formate to CO2, with the equilibrium on the site of formate oxidation. It is a hexameric molybdoenzyme with a (abg)2 structure which is localized in the cytoplasm. It belongs to the group of NAD+ dependent FDHs with coordination of a molybdenum containing cofactor (bis-MGD form) in its active site showing tolerance with oxygen. Several FeS clusters are coordinated in RcFDH (5x Fe4S4, 2x Fe2S2) bridging electron transfer from molybdenum to the flavin mononucleotide site, which uses NAD+ as physiological electron aceptor. Heterologously expressed RcFDH in E. coli shows high activities for formate oxidation. The back reaction for CO2 reduction is possible with RcFDH, however, at significantly slower rates. Site-directed mutagenesis studies show the importance of amino acid residues at the active site for substrate conversion. These studies give insight in the reaction mechanism which are useful for the generation of an effective CO2 reductase in the future.

12:00-12:25 Axel Magalon
Laboratoire de Chimie Bactérienne, CNRS, Aix Marseille Université, Marseille'Sulfuration of the MO center of formate dehydrogenases is essential for conversion of formate to CO2

In a context of limited fossil fuel resources and because of the need to restrict emissions of CO2, the main green-house effect gas, it is essential to develop research for CO2 valorization. One of the most promising ways is to transform this compound in more reduced forms of carbon that can be used to generate hydrocarbons. Despite its inherent high stability, some microbial enzymes are able to perform the reversible reduction of CO2 into formate, in mild conditions and with a high efficiency. These enzymes, formate dehydrogenases, contain a molybdenum active site where the catalytic reaction occurs. Nevertheless, complete understanding of the catalytic reaction has yet been hampered by an undefined coordination sphere of the Mo center. Here, we report the discovery of a sulfur-activation step of the Mo atom that is essential for enzyme reactivity. Mechanistic details of this process sustained by a dedicated protein for formate dehydrogenases, FdhD, will be provided.

Lunch (buffet, salle des actes)

3rd session. Chair: Elizabeth Lojou

14:00-14:25 Oliver Lenz
Institute of Chemistry, Technische Universitaet Berlin
"Biocatalytic H2 conversion in the presence of O2".

Hydrogenases are natures’s catalysts dedicated to the rapid and reversible oxidation of H2 into protons and electrons. They are considered as promising tools in renewable energy technologies. Most hydrogenases are, however, readily inactivated by O2. Fortunately, certain [NiFe] hydrogenases, including the four [NiFe]-hydrogenases from the soil bacterium Ralstonia eutropha, have evolved remarkable tolerance towards O2 and enable their host organisms with the ability to utilize H2 as energy source at high O2 partial pressure. The structural and catalytic features that enable these enzymes to sustain activity in the presence of O2 will be discussed.

14:25-14:50 Christophe Léger
Laboratoire de bioénergétique et ingénierie des Protéines, Marseille
"Investigations of the mechanism of FeFe hydrogenases: catalysis and inhibition."

I will present recently published data related to the mechanism of H2 oxidation and evolution by FeFe hydrogenase, which combine electrochemical studies of the WT enzymes from C. acetobutylicum and C. reinhardtii and site-directed mutants, and results from theoretical calculations (DFT, MD). This will illustrate the interdisciplinary approach we use, which is the result of a long-term collaboration with the labs of H. Bottin (CEA, Saclay, F), Ph Soucailles (INSA, Toulouse, F), L. de Gioia (Univ. Milan, I) and J. Blumberger (UCL, London, UK) [1-6].

[1] V Fourmond et al, "The oxidative inactivation of FeFe hydrogenase reveals the plasticity of the H-cluster" Nature Chemistry (2014); [2] V Hajj et al, “Reductive inactivation of FeFe hydrogenase and implication for catalysis” Energy and Environmental Science 7 715 (2014); [3] V. Fourmond, et al, “Steady-state catalytic wave-shapes for 2-electron reversible electrocatalysts and enzymes” J. Am. Chem. Soc. 125 3926 (2013); [4] T. Miyake et al, “Does the environment around the H-cluster allow coordination of the pendant amine to the catalytic iron center in [FeFe] hydrogenases? Answers from theory” J Biol Inorg Chem 18 693 (2013); [5] C. Baffert et al, “Covalent attachment of FeFe hydrogenases to carbon electrodes for direct electron transfer”, Anal. Chem. 84 7999 (2012); [6] C Baffert et al “CO disrupts the reduced H-cluster of FeFe hydrogenase. A combined DFT and PFV study” J. Am. Chem. Soc. 133 2096-2099 (2011)

14:50-15:15Ulla Wollenberger
Universität Potsdam, Analytische Biochemie, Potsdam
"Bioelectrocatalytic reactions of molybdo- and heme proteins and biosensor application"

Bioelectrocatalysis involves the enhancement of an electrode reaction by a (bio) catalytic process and is thus the basis for sensitive and selective electroanalytical devices.  For effective bioelectrocatalysis it is essential to achieve a fast communication between the redox protein and the electrode, while the biocatalytic activity is preserved.  The signal transduction is performed by direct electronic communication between the protein and redox electrodes and by mobile or polymer bound redox mediators. We are using such approaches to contribute to the understanding of the mechanism of enzymes and their biotechnological exploitation.  Examples of such electrochemical biosensors involve cytochrome c and peptides on self assembled monolayers,  human sulfite oxidase on nanoparticles, and polymer bound  E.coli aldehyde oxidoreductase. Potential technological applications are discussed.


15:15-15:40 Olga Iranzo
Institut des Sciences Moléculaires de Marseille, Aix Marseille Université, CNRS, Marseille, France
"Fine-tuning the Structure of His-containing Peptides for Copper Binding"

Designing small peptides capable of binding Cu(II) mainly by the side chain functionalities and forming single species in the neutral pH range is a hard task since the amide nitrogens strongly compete for Cu(II) coordination [1]. However, metalloproteins are proficient on this and generate the appropriated coordination pocket to avoid amide coordination. This exquisite control allows copper proteins to attain a myriad of catalytic activities and thus, a large variety of biological functions [2]. Achieving this with short peptides will be very appealing to engineer miniaturized copper proteins with potential redox and hydrolytic activities. Recently, we have designed two His-containing decapeptides, a cyclic (C-Asp) and an open derivative (O-Asp), capable of coordinating Cu(II) [3]. Potentiometric, mass spectrometric and spectroscopic studies indicate that at 1:1 Cu(II)/peptide ratio these peptides form similar single Cu(II) species at close to neutral pH values and that Cu(II) is exclusively coordinated by the side chain functionalities [3,4]. Interestingly, different redox properties were observed for these similar species due to the distinct intrinsic nature of their peptidic scaffolds. Possible consequences of all these findings in catalysis will be discussed.

[1]. a) Sigel H; Martin R. B. Chem. Rev. 1982, 82, 385-426. b) Kozłowski H.; Bal W.; Dyba M.; Kowalik-Jankowska T. Coord. Chem. Rev. 1999, 184, 319-346. [2] a) Holm R. H.; Kennepohl P.; Solomon E. I. Chem. Rev. 1996, 96, 2239-2314; b) Gaggelli E.; Kozłowski H.; Valensin D.; Valensin G.; Chem. Rev. 2006, 106, 1995-2044. [3] Fragoso A.; Lamosa P.; Delgado R.; Iranzo O. Chem. Eur. J., 2013, 19, 2076-2088. [4] Fragoso A.; Delgado R.; Iranzo O. Dalton Trans., 2013, 42, 6182-6192.

coffee

4th session. Chair: Marius Réglier

16:10-16:35 Christian Limberg
Humboldt-Universität zu Berlin, Institut für Chemie, Berlin
"Biomimetic complexes modeling non-heme iron dioxygenases"

The lecture will deal with the synthesis and investigation of low-molecular weight analogues for the active sites of non-heme iron dioxygenases, such as the acetyl acetone dioxygenase [1] and the cysteine dioxygenase [2]. The (His)3-coordination spheres of the FeII centers within these enzymes were simulated by tris(pyrazolyl)borate (TP) ligands and the Tp-iron(II)-substrate complexes were studied with respect to their O2 reactivity. Structural and mechanistic information is deduced from the results.

[1] I. Siewert, C. Limberg, Angew. Chem. Int. Ed. 2008, 47, 7953-7956. [2] M. Sallmann, I. Siewert, L. Fohlmeister, C. Limberg, C. Knispel, Angew. Chem. Int. Ed. 2012, 51, 2234–2237.

16:35-17:00 Jalila Simaan
Institut des Sciences Moléculaires de Marseille, Aix Marseille Université, CNRS, Marseille, France
"Mechanistic investigation of a non-heme iron(II) containing enzyme: ACC Oxidase"

The gaseous plant hormone ethylene regulates many processes of plant development and defense as, for example , germination, fruit ripening and senescence. ACC Oxidase (ACCO) catalyzes the last step of ethylene biosynthesis in plants. The substrate, 1-Aminocyclopropane carboxylic acid (ACC), is converted into ethylene in the presence of dioxygen and a reductant. In addition, for unclear reasons, carbon dioxide (or hydrogenocarbonate) is required for maximum activity. Thanks to an interdisciplinary approach we aim at getting more information on this enzyme combining mutagenesis, kinetic, modeling and spectroscopic studies [1] with the preparation and the study of model complexes [2].

[1] Brisson, El Bakkali-Taheri et al. J. Biol. Inorg. Chem., 2012 , 17, 939–949 [2] a) Ghattas, et al. Inorg. Chem 2008, 47(11), 4627 –4638 b) Ghattas et al., Inorg. Chem. 2009, 48, 3910-3912 c) Baráth et al., Chem Commun. 2010, 46, 7391–7393

17:00-17:25 Matthias Driess
Technische Universität Berlin, Department of Chemistry: Metalorganics and Inorganic Materials, Berlin
"Bioinspired Inorganic Synthesis: Progress in Artificial Water Oxidation and Oxygen Reduction Catalysis"

Artificial photosynthesis is currently considered to be one of the most convenient ways to convert solar energy into chemical energy. Photosynthesis offers an efficient model for designing artificial solar energy conversion system for clean fuel generation. In nature, oxidation of water to oxygen, which is a four electron and four proton transfer process, takes place in the photosystem II (PS II) at the oxygen evolving centers (OECs) of Mn4CaO5 clusters. Inspired by the principles of nature and driven by the vital need to develop robust and efficient water oxidation catalyst, continuous efforts have been made to establish functional mimics of the OECs. Although, numerous biomimetic water splitting catalysts based on noble metals complexes, organometallics and inorganic metal oxides have been shown to be functional but until now, none of them have proven to be effective with good efficiency for water oxidation and moreover for overall water splitting. More efforts are needed to enable a better control on different key parameters (e.g. oxidation state of the OECs) of suitable and robust inorganic photocatalysts. Over the last few years, our group has given significant attention and contribution to the molecular single-source precursor (SSP) concept for the formation of homo- and heteropolymetallic oxides. The main advantages of using this route instead of the ‘classical’ precipitation method involving multiple components as precursors are the relative low temperature synthesis, precise control on the composition with a maximum of dispersion of the elements on the atomic level and of the oxidation states of the metals in the system. Recent progress in the synthesis of multifunctional metal oxide catalysts from molecular precursors for efficient water oxidation and oxygen reduction will be discussed in my talk.

17:25-17:50 Cyril Bressy
Institut des Sciences Moléculaires de Marseille, Aix Marseille Université, CNRS, Marseille, France
"How Small Organic Molecules could act as Mimic of Enzyme? Studies in Enantioselective Organocatalytic Acyl Transfer" 

Organocatalysis [1] emerged quite recently as an alternative to metallo- and biocatalysis. In the field of enantioselective catalysis, organocatalysis gained in the past years a huge interest from organic chemists. In order to reach a high level of efficiency to rapidly obtain complex building blocks useful in synthesis, we decided to use this type of catalysis for desymmetrization processes of meso compounds [2]. We focused our efforts to prepare densely functionalized tetrahydropyrans [3], heterocyclic moieties present in many biologically active natural products. The results concerning two major classes of chiral organocatalysts able to promote enantioselective acyl transfer will be presented: dialkylaminopyridines (DMAP) [4] and isothioureas [5]. Many interesting parallels about the mode of action could be made between this last class of organocatalysts and lipases.

[1] Comprehensive Enantioselective Organocatalysis: Catalysts, reactions, and Applications, 3 Vol., P. I. Dalko Ed. Wiley-VCH, Weinheim, 2013. [2] a) A. Enriquez-Garcia, E. P. Kündig, Chem Soc. Rev. 2012, 41, 7803-7831; b) M. D. Diaz-de-Villegas, J. A. Galvez, R. Badorrey, M. P. Lopez-Ram-de-Viu, Chem. Eur. J. 2012, 18, 13920-13935. [3] M. Candy, G. Audran, H. Bienaymé, C. Bressy, J.-M. Pons, Org. Lett. 2009, 11, 4950-4953. [4] C. Roux, M. Candy, J.-M. Pons, O. Chuzel, C. Bressy, Angew. Chem. Int. Ed. 2014, 53, 766-770. [5] V. B. Birman, X. Li, Org. Lett. 2006, 8, 1351-1354.