Overview

The beginnings of this conference series date back to 2003, initialised by a nebulous idea. This idea became concrete through the lectures and discussions at the Beilstein Bozen Symposium 2002 - Molecular Informatics: Confronting Complexity. In preparation for this symposium, the organisers, Martin Hicks and Carsten Kettner, stated in the overview [1] that "the flood of information generated as a result of research in genomics and proteomics is often completely overwhelming", which makes it inherently difficult to use this information for analysis, confirmation, interpretation, and even to understand the experimental results and to distinguish between real findings and assumptions. As much of the experimental data is reused for model development, e.g., in systems and structural biology and in drug discovery and targeting, there is a requirement to ensure accuracy and contextual quality of this data. Contextual data is data that describes the experimental data with unambiguous attributes and is now called metadata.

An international panel of molecular informatics researchers presented results of their analysis and understanding of the storage, processing and distribution of information encoded by molecules and molecular interactions, including protein structure, pattern recognition, drug discovery, design and delivery, and software tools for analysis and prediction. A unifying theme throughout the workshop was the goal of gaining insight into the behaviour of biological and molecular systems through computer simulations.

From the energetic discussions that followed the presentations, it quickly became clear that the software tools presented could only run successfully with very well defined data sets. It also became clear that the limitations in data quality were preventing researchers and modellers from generating knowledge that went significantly beyond hypotheses. Even subsequent data-driven research was considered ineffective, if not impossible.

It is a small step from structural proteomics to enzymology (and biocatalysis). Enzymologists monitor the activities of enzymes and obtain metrics such as reaction rates, substrate specificities and enzyme efficiencies. The outcome of the discussions with researchers during the symposium and with other biochemists, particularly enzymologists, after the symposium reinforced Carsten's personal experience of the limitations encountered while characterising the kinetics of membrane-bound ion transporters: it was almost impossible to comprehensively interpret published kinetic data to corroborate one's own findings, as incomplete descriptions of the methodology precluded matching the experimental data.

Encouraged, in particular by Athel Cornish-Bowden (BIP-CNRS, Marseille), Rolf Apweiler (EBI, Cambridge) and Friedrich Lottspeich (MPI for Biochemistry, Martinsried), Carsten proposed the organisation of a workshop to the directors of the Beilstein-Institut. The aim of this workshop was to confirm the prevailing opinion that standardisation of experiments and methods for the comprehensive characterisation of enzymes is necessary and that initial suggestions should be presented to the general scientific community. This workshop had he unwieldy name “ESCEC – Experimental Standard Conditions of Enzyme Characterizations” and took place at the Hotel Jagdschloss Niederwald Hotel in October 2003. The goal was surpassed by the end of a round table discussion where several participants, including Rolf Apweiler, Athel Cornish-Bowden, Jan-Henrik Hofmeyr, Thomas Leyh, Dietmar Schomburg, and Keith Tipton, spontaneously agreed to work out a proposal for standards. This working group constituted itself as the STRENDA Commission in February 2004 [2].

In parallel, Carsten laid the groundwork for the STRENDA Commission when he analysed the data deposited in BRENDA relating both the experimental conditions and the experimental results of the key enzymes of the glycolysis of four well-studied model organisms [3]. The result was sobering: although these three enzymes had been well investigated with respect to their structures and sequences, the kinetic data was incomplete and showed wide ranges for some parameters. Although the experimental studies had been carried out by seemingly comparable methods, crucial differences stood out where the methods were comprehensively described (which was rarely the case). Similarly, to the lack of functional data making it nearly impossible to numerically analyse metabolic pathways, cells, tissues or entire organs [4], those observations clarified the dilemma of enzymology: “the purpose of enzymology is to bring about advances in the understanding of enzymes through enzyme characterisation, but in doing so it generates large quantities of data, the value of which is limited by the lack of standard experimental procedures.” [3]. The standardisation of procedures crucial as experiments are carried out in different laboratories under different conditions. In his epilogue on the Beilstein Bozen Symposium 2002, Gisbert Schneider (today ETH Zurich) described this finding in plain language: “The choice of methods and objects strongly depends on the scientific background and individual skills of a researcher.” [5].

Despite its importance, the STRENDA Commission quickly recognised that standardisation of experimental procedures was a problem that could not be satisfactorily solved in a short timeframe. The Commission therefore approached the challenge from the opposite direction: it developed guidelines for reporting enzymology data, namely the STRENDA Guidelines which are now recommended by more than 55 biochemistry journals [6,7] and which form the basis of STRENDA DB, a web-based database whose data submission form automatically checks the manuscript data for compliance with the STRENDA Guidelines before or during the publication process [8]. However, this is a story that will be presented later during this conference.

Since 2003, this conference series has been held every two years. In 2011, it was renamed the Beilstein Enzymology Symposium. With this renewed focus, and with the help of the co-organisers, the Beilstein Enzymology Symposia embrace structural, computational and biological disciplines, and bring together established and early career researchers to discuss the diverse roles of enzymes in biology, and to explore the limitations and challenges of holistic studies that attempt to integrate microscopic views of protein function into complex biological behaviour.

With this symposium, the organisers will not only celebrate the 20th anniversary of this series along with all participants, but will also span the arc from the history of enzymology and its impact on the past, present and the future of the study of enzyme mechanisms, through current insights into enzyme mechanisms and regulation, as well as directed/engineered and natural evolution of enzyme functions, to the computational prediction of structures and functions, and the application of this combined knowledge to the investigation of reaction cascades and their use in biotechnology.

All participants are encouraged to discuss their latest results, approaches and methodologies in experimental, theoretical and computational enzymology.

Enjoy the Symposium!

[1] https://www.beilstein-institut.de/en/symposia/archive/bozen/bozen-2002/

[2] https://www.beilstein-institut.de/en/projects/strenda/

[3] Kettner, C., and Hicks, M.G. (2005) The Dilemma of Modern Functional Enzymology. Current Enzyme Inhibition 1(2):3-10. DOI:10.2174/1573408054022234.

[4] Stelling, J., Klamt, S., Bettenbrock, K. et al. Metabolic network structure determines key aspects of functionality and regulation. Nature 420:190–193 (2002). DOI:10.1038/nature01166.

[5] Schneider, G. (2003) Epilogue – Complexity Challenges Research in Molecular Informatics. In: Proceedings of the Beilstein Bozen Symposium – Molecular Informatics: Confronting Complexity. Eds. M. Hicks & C. Kettner. Logos Verlag Berlin. https://www.beilstein-institut.de/download/750/schneider_3.pdf.

[6] Apweiler, R., Cornish-Bowden, A., Hofmeyr, J.-H.S., Kettner, C., Leyh, T.S., Schomburg, D. and Tipton, K.T. (2005) The importance of uniformity in reporting protein-function data. Trends Biochem. Sci. 30:11-12. DOI:10.1016/j.tibs.2004.11.002

[7] https://www.beilstein-institut.de/en/projects/strenda/guidelines/, and Tipton, K.F., Armstrong, R.N., Bakker, B.M., Bairoch, A., Cornish-Bowden, A., Halling, P.J., Hofmeyr, J.-H.S., Leyh, T.S., Kettner, C., Raushel, F.M., Rohwer, J., Schomburg, D., Steinbeck, C. (2014) Standards for Reporting Enzyme Data: The STRENDA Consortium: What it aims to do and why it should be helpful. J. PiSc. 1:131-137. DOI:10.1016/j.pisc.2014.02.012.

[8] Swainston, N., Baici, A., Bakker, B.M., Cornish-Bowden, A., Fitzpatrick, P.F., Halling, P., Leyh, T.S., O'Donovan, C., Raushel, F.M., Reschel, U., Rohwer, J.M., Schnell, S., Schomburg, D., Tipton, K.F., Tsai, M.-D., Westerhoff, H.V., Wittig, U., Wohlgemuth, R. and Kettner, C. (2018) STRENDA DB: enabling the validation and sharing of enzyme kinetics data. The FEBS J. 285(12):2193-2204. DOI:10.1111/febs.14427.