From Enzymology to Systems Biology and Back
Beilstein ESCEC Symposium 2015

14 18 September 2015

Hotel Jagdschloss Niederwald, Rüdesheim, Germany


The Beilstein ESCEC Symposium 2015 brought together biochemists, enzymologists and systems biologists with experts in bioinformatics and computer sciences. The Scientific Program was very well attended and the speakers addressed a wide range of topics to draw the path from enzymology to systems biology - and occasionally even back.

Both the summary and the photo gallery give an impression of the symposium's atmosphere.

Topics 2015

  • Enzyme mediated cascade reactions

  • Protein engineering by directed evolution and/or rational design

  • Metabolomics and systems biology

  • Application of systems biology in the "coloured" biotechnologies (green, red, blue)

  • Manufacturing of chemical products using biocatalysis

  • Data analysis, storage and sharing

 

Summary

by Elisabeth Davioud-Charvet, Université de Strasbourg, France and

Peter Halling, University of Strathclyde, Glasgow, UK

 

The ESCEC symposia brought together the scientific communities working in biological chemistry, and enzymology to systems biology (and even back). Established and younger researchers from a wide range of areas - often outside chemistry - were invited to present the most advanced aspects of their work, with the aim of enhancing interdisciplinary communication and sharing new ideas and inspirations.

Enzymology

Pedro Martins (Porto) described a new mathematical treatment of the simple Henri-Michaelis-Menten-Briggs-Haldane kinetic network, avoiding the steady-state and other approximations. Oliver Ebenhöh (Dusseldorf) presented an investigation of starch synthesis and degradation processes along with mechanistic aspects of the enzymic reactions taking place at the granule surface. Amnon Kohen (Iowa) showed the value of measuring kinetic isotope effects, their temperature dependence, in understanding enzyme mechanisms. Shelley Copley (Boulder) showed how evolutionary change can be rapid and effective in microrganisms. Reinhard Sterner (Regensburg) described an enzyme, whose sequence was expected to be similar to that found in the last universal common ancestor. It functioned as an apparently quite sophisticated enzyme, suggesting that many fundamental properties had already been near optimised some 4 billion years ago. Manfred Konrad (Göttingen) presented a different practical application of enzymes in medicine, i.e. L-asparaginase as an effective treatment for various leukemias. Douglas Auld (Cambridge) presented the misinterpretation issue raised by high throughput inhibitor screening using luciferase-based reporter-gene assays for drug discovery. The comprehensive analysis allowed to set up dual luciferase-based reporter gene assays. Christian P. Whitman (Austin) reviewed the kinetic/structural/evolutionary mechanism of the hydratase-aldolase-enzymes of the bacterial meta fission pathway. Ming-Daw Tsai (Taipei) presented detailed studies on a viral DNA polymerase displaying significant mutagenic formation of G:G base pairs. Friedrich Förster (Martinsried) developed an algorithm for cryoelectron tomography to classify and then average shapes of different particles to study the function of large complexes (ribosome and proteasome).

Biocatalysis has emerged as a new field between modern enzymology and green chemistry. A session was dedicated to the most recent advanced biocatalytic processes for large scale preparation of valuable compounds of interest. Selection of enzyme variants as biocatalysts is the challenge of modern industry to produce valuable pharmaceuticals and agrochemicals, with high chemo-and stereo-selectivity, by low cost and green chemistry.

Daniel Mink (Geleen) reviewed the industrial enzymatic C-C bond biotransformations used by DSM Company for the cost-effective manufacturing of homochiral buiding-blocks. Selected key examples were presented to illustrate how the platform of biosynthetic engineering of wild-type enzymes can select mutants to build C-C bonds with high enantio- and diastero-selectivity from cheap chemicals under mild conditions. In the same vein, Dörte Rother (Jülich) showed how the combination of three classes of enzymes (wild-type and variants), catalyzing multi-step reactions in cascade, can be used to produce chiral buiding-blocks in a high yielding modular approach from inexpensive starting chemicals. Anthony Green (Manchester) presented examples of synthetic routes to produce high-value bio-inspired chemicals applied to natural product and medicinal chemistry.

Metabolomics, Proteomics, and Systems Biology are the emerging fields to study the complexity of large networks in individual cells and tissues, organs and in the whole organisms.

Monica Campillos (München) showed how new approaches to study systems biology of small molecules led to significant insights on the comprehensive interplay between mode of action of drugs – their phenotypic effects – and their roles in diseases. From various databases of small molecules, analysis of chemical genetics data allowed prediction of drug side-effects by integration of drug symptoms related to disease symptoms, of mouse genes related to mouse phenotypes, and disease symptoms related to drug-gene relationships. Barbara M. Bakker (Groningen) demonstrated how molecular competition at the enzyme level of the fatty acid oxidation pathway might explain the patient physiology with severe fatty-acid disorders found in the metabolic syndrome. Johann M. Rohwer (Stellenbosch) showed how modeling redox networks place the kinetics of cellular redox processes into a systems biology context. Redox systems should be modeled as redox couples with mass action model. Ulrike Kusebauch (Seattle) developed the recent advances in mass spectrometry techniques, resources, and tools to allow comprehensive quantitative proteomics. Olaf Wolkenhauer (Rostock) opened our horizons with the modeling of life complexicity at multi-levelness applied to the self-organization of the tissues. There is a functional organization of the tissues via interplay between gene, cell and tissue functions, which governs a progressive cell-to-tissue determination (emergence), and regressive determination coordination.

Photo Gallery

Please click on the pictures to either enlarge or to start the slideshow.

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Speakers

 

Karen N. Allen / Boston University, USA
Specificity and promiscuity in enzyme superfamilies

Douglas S. Auld / Novartis Institutes for Biomedical Research, Cambridge, USA
Impact of luciferase reporter enzymes on drug discovery efforts

Barbara M. Bakker / University Medical Center Groningen, The Netherlands
Living on the edge: molecular competition explains loss of robustness in fatty-acid oxidation disorders

Monica Campillos / Helmholtz Zentrum München, Germany
Systems biology of small molecules

Shelley D. Copley / University of Colorado Boulder, USA
E. coli can navibate a rugged fitness landscape to reconstitute PLP synthesis within 320 generations after deletion of pdxB: How?

Oliver Ebenhoeh / Heinrich Heine University Düsseldorf, Germany
Optimality principles in plants: towards synthetic starch

Friedrich Förster / Max Planck-Insitute of Biochemistry, Martinsried, Germany
Analyzing the co-translational protein translocation machinery in situ using cryo-electron tomography

John A. Gerlt / University of Illinois, Urbana, USA
Enzyme Function Initiative: tools and strategies for discovering novel enzymes & metabolic pathways

Anthony Green / The University of Manchester, UK
Biocatalytic retrosynthesis: redesigning synthetic routes to high-value chemicals

Henning Hermjakob / European Bioinformatics Institute, Cambridge, UK
The Reactome pathways portal

Amnon Kohen / University of Iowa, Iowa City, USA
The enigmatic conservation of enzyme dynamics in evolution

 

 

 

Manfred Konrad / Max Planck-Institute for Biophysical Chemistry, Göttingen, Germany
Enzymatic activities in microcapsules and microfluidic droplets

Ulrike Kusebauch / Institute for Systemsbiology, Seattle, USA
Development of comprehensive quantitative proteome resources

Pedro M. Martins / University of Porto, Portugal
In search of lost time constants and non-Michaelis-Menten parameters

Daniel Mink / DSM Innovative Synthesis B.V., Geleen, The Netherlands
Industrial enzymatic C-C bond formation

Frank M. Raushel / Texas A&M University, College Station, USA
Finding homes for orphan enzymes

Johann M. Rohwer / University of Stellenbosch, South Africa
Modelling redoxin networks: Placing the kinetics of cellular redox processes into a systems biology context

Doerte Rother / Forschungszentrum Jülich, Germany
Modular synthetic enzyme cascades for the production of pharmaceutically potent chiral building blocks

Reinhard Sterner / University of Regensburg, Germany
Evidence for the existence of elaborate enzyme complexes in the LUCA era

Ming-Daw Tsai / Academia Sinica, Taipei, Taiwan
How some low-fidelty DNA polymerases choose non-Watson-Crick from Watson-Crick incorporation

Christian P. Whitman / The University of Texas at Austin, USA
The hydratase/aldolase-catalyzed reactions in the bacterial degradation of polycyclic aromatic hydrocarbons: analysis and implications

Olaf Wolkenhauer / University of Rostock, Germany
Abstraction as an approach to infer organizing principles from cellular processes