The 6th Novel Enzymes conference sequel took take place from 9-12 October 2018, at the Technische Universitaet Darmstadt, Germany, in the historical "Maschinenhaus“ (see image), a beautiful architectural monument built in 1904 as a university power plant, and recently renovated to hold a lecture theatre and seminar rooms.
This event brought together 200 scientists from both academia and industry, coming from 30 countries and four continents: Europe, the Americas, Asia and Australia –, to present the state of the art in enzymology and biocatalysis. From discovery and engineering of enzymes to novel biocatalytic routes and products, researchers attempt to mimic and tailor nature’s toolbox of biocatalysts: Their applications in White Biotechnology and in Green Chemistry have the potential to improve human life; to minimise the use of hazardous substances and energy expenditure in the chemical industries; to enable sustainable production processes; to aid environmental clean-up. By combining molecular biology, protein engineering and chemical analysis, enzymes today can be significantly improved or even given entirely new properties and functions. For example, enzymes can be created that can tolerate organic solvents, perform entirely new type of chemistry unseen in nature or be made resilient and suitable for demanding industrial applications.
The conference chairman, Wolf-Dieter Fessner, Professor of Organic Chemistry at the Technische Universitaet Darmstadt, opened the conference. In his welcome address he gave an overview of the need for advanced sustainability in the chemical synthesis, and the potential of biocatalysis science to accelerate such a change, as well as the challenges and potential solutions to be found: through the development of the next generation catalysts– Novel Enzymes – targeted to specific tasks, along with their application and impact in industry and in addressing societal challenges.
Biocatalysts face some limitations with respect to technical applications, which can be overcome by “tailoring” them to the specific task. Enzymes have the potential to catalyse chemical reactions precisely, stereoselectively, with high speed and yield and under mild conditions.However, often chemical bonds of interest aren’t made by any natural enzyme. In addressing this challenge, as outlined by Professor Fessner, a variety of strategies and tools to identify or tailor enzymes to specific tasks have been developed:
1) Prospecting in Nature:
a) screening of microorganism collections
b) screening of organisms from new habitats
c) screening of ambient DNA (metagenomics)
2) Screening of genetic information in silico from accumulated databases
3) Optimization of known enzymes
a) by rational protein engineering or
b) by directed evolution in vitro
Professor Fessner also highlighted that this year´s one half of the Nobel Prize in Chemistry was to be awarded “for the directed evolution of enzymes“. In directed evolution experiments scientists provide a new niche in the laboratory, so to speak, and encourage the evolution of enzymes to catalyze commercially useful reactions. The selection of the topic for awarding highest academic honors shows how important this science is for the future of humanity he said, and quoted Prof. Frances H. Arnold, the designated Nobel prize winner for saying:
“The future of biocatalysis is no longer limited by our ignorance, it’s really only limited by our imaginations”.
The second speech was a welcome address from the university´s vice president, during which he introduced the history, the core strengths and future goals of the TU Darmstadt. He also mentioned that Darmstadt is known as the “City of Science” named so because more than 30 research and scientific institutions and high-technology companies are located in the city. Among them is the European Space Operations Centre, the GSI Helmholtz Centre for Heavy Ion Research and three Fraunhofer Institutes. The TU Darmstadt cooperates closely with many of these establishments.
Following the welcome note, the main scientific programme of the Novel Enzymes conference started, addressing several of the challenges the scientists are presented with when searching for an appropriate, targeted biocatalyst. Moreover, the potential breadth of synthesis applications that can unfold when novel enzymatic properties are found or generated was presented through several lectures. Among the many topics presented were the following:
- The power of the concept of Biocatalytic Retrosynthesis - in which molecules are disconnected with a view to using biocatalysts in the key bond forming steps and then designing entire synthetic route cascades using the ever expanding biocatalytic toolbox, for the production of high value pharmaceuticals (Prof. N. Turner, University of Manchester).
- Recent advances in the discovery, engineering and application of monooxygenases after a new class of P450 monooxygenases from metagenomic marine bacteria was discovered from the north sea, that play a central role in the degradation of algal carbohydrates. Algae represent a massive environmental challenge, especially during their bloom and this newly discovered P450 can be key to controlling algal eutrophication and avoid the multiple environmental problems it causes (Prof. U. Bornscheuer, Greifswald University).
- Building diverse alkaloids in a one-pot, high yield cascade and accessing novel spirocompounds by using a hitherto undiscovered activity of a synthetic plant enzyme, (S)-norcoclaurine synthase (Prof. J. Ward, UCL London).
- Interfacing between experimental methods and computational predictions of dynamic phenomena of substrate binding for targeted enzyme engineering (Prof. J. Pelletier, Université de Montréal).
- Exploring the natural enzyme biodiversity from metagenomics resources to find the perfect catalysts for synthesising targeted molecules for cost-competitive sustainable industrial applications and promoting a circular economy (Dr J. Mampel, BRAIN AG).
- Using novel carboligases (created by combining metagenomic screening and directed evolution techniques) for asymmetric synthesis and assembly of novel reaction cascades, as well as towards producing valuable product families with potential use in industrial manufacturing processes (Prof. P. Clapés, Catalonia Institute for Advanced Chemistry).
- Halohydrin dehalogenase biocatalysis revisited: New enzymes, their substrate selectivities and novel catalytic functionalities (Prof. A. Schallmey, Technische Universtät Braunschweig).
- Analysis of biosynthetic pathways as a starting point for the identification of uncommon enzymatic transformations:Biocatalysis can offer diversity-oriented synthesis, alternative solutions to challenging reactions, natural products arising from little related pathways or intermediates, high probability of bioactivity of the new products (Prof. M. Mueller, University of Freiburg).
- New enzymes and chemoenzymatic reaction cascades for asymmetric synthesis of a wide variety of aminocarboxylic acids: Illustration of how chemocatalysts, natural enzymes and designed artificial biocatalysts can be combined in multistep syntheses of pharmaceuticals, vitamins, and biodegradable metal chelators. (Prof. G. Poelarends,University of Groningen).
- Using directed evolution of enzymes and bioinformatics tools to develop directed evolution schemes, to rationally design complex enzyme systems for optimal performance in synthesis. Designing methods to assemble them effectively from cell free extracts for a self-assembling artificial metalloenzyme capable of orthogonal biochemistry and aiming to incorporate and harness those in intracellular metabolism (Prof. S. Panke, ETH Zurich).
- Biohybrid Catalysts: How redesigning proteins for innovations can lead to novel catalysts, novel products selectivities, efficiencies, flexibilities, decreased energy demands and less toxic by-products (Dr D. Sauer, RWTH Aachen).
- Expanding the toolbox of redox biocatalystsfor the conversion and production of alcohols. Strategies for generating novel robust oxidative enzymes, that outperform existing/known biocatalysts and application of oxidative enzymes on industrial scale (Prof. M. Fraaije, University of Groningen).
- Exploitation of highly stereoselective phenolic acid decarboxylases to perform the enzymatic carboxylation of styrene-type substrates (reactions not feasible by chemical methodology) as well as promiscuous catalytic activities for asymmetric hydratation of the C=C bond of with high enantiomeric excess (Prof. K. Faber, University of Graz).
Two dozen other lectures on various aspects of novel enzymes were delivered, which were chosen by the Novel Enzymes Committee from a pool of triple the size of submitted abstracts, which indicates the high profile that this conference series has gained in the scientific community. Remarkably, two lectures were presented by young entrepreneurs, who focused on novel bioinformatics tools and technologies available for enzyme design and catalytic activity predictions:
- Mining structural databases employing the “Catalophore Computational Platform”. This newly developed technology presents a practical tool, offering the possibility to search for as yet undiscovered enzyme activities and for the development and engineering of novel biocatalysts - also for non-natural reactions independent on sequence and structural similarity (Dr C. Gruber, Innophore Enzyme Discovery).
- The 3DM informationsystems are protein super-family platforms that collect, combine and integrate many different types of protein-related data. 3DM systems are designed to facilitate the exploration of sequence-structure-function relations, and can be successfully used to elucidate the function of individual amino acids and predict the effects of mutations, among others (Dr H.-J. Joosten, BioProdict).
The Novel Enzymes Conference hosted an extended poster session with posters being displayed over the entire duration of the conference. Two specific sessions were dedicated to browsing through them and getting acquainted with new discoveries, concepts and technologies, mostly presented by younger scientists. From an excellent pool of 97 scientific posters three were chosen by the Novel Enzymes Committee for their outstanding quality and their scientific concept, and were awarded the following prizes:
1st poster prize, the PROZOMIX Grand Poster Award of €1000 for the best contribution to the science of “Novel Enzymes.” The award went to poster author Caroline Paul from Delft University of Technology for “Synthetic cofactors for redox biocatalysis: scope and challenges of monooxygenases“.
2nd poster prize, a subscription to the RSC journal Green Chemistry. The award went to poster author Carine Vergne-Vaxelaire, from Université Paris-Saclay for “A family of Native Amine Dehydrogenases for the Asymmetric Reductive Amination of Ketones“.
3rd poster prize, a subscription to the RSC journal Catalysis Science and Technology. The award went to poster author Matthieu Da Costa from Ghent University, for “Exploring the scope of nickel pincer as enzymatic cofactor: engineering of gluconate epimerase towards the production of rare sugars“.
At the last evening of the conference a dinner took place in a traditional German restaurant where all participants had the opportunity to taste the local cuisine and brewery specialties, and perhaps have some inspiring discussions and interactions with co-workers and collaborators in an informal, relaxed atmosphere.
We would like to thank our kind and generous Novel Enzymes sponsors, namely the following companies: Bio-Prodict, PROZOMIX, BASF, MERCK, Innophore, and TWIST Bioscience, who provided for some of the more fun aspects of the conference and for the poster prizes, as an encouragement and small reward to the young aspiring scientist who presented those posters.
The Novel Enzymes conference partners were the EU Horizon 2020 projects CarbaZymes and Robox, EraCoBioTech, and the media partners Royal Society of Chemistry journals Green Chemistry and Catalysis Science and Technology.
The Novel Enzymes conference provided a great opportunity for the experts in the field and the younger generation of scientists to network and foster further collaborations which will accelerate discoveries in this critical and fast developing area of biotechnology: Termed by the European Commission “Key Enabling Technology“ for the 21st century, due to the huge innovative potential it holds for improving industrial processes, and for producing much in need medicines, chemicals and fuels that will help us underpin a shift to a greener, environmentally conscious and more resource-efficient economy.
This year´s Novel Enzymes, happily coinciding with the Nobel Prize in chemistry 2018 announcement on one of the conferences core topics, emphasized the giant leaps taken in enzyme discovery and engineering within the last two decades, and the huge potential the technology holds for multifaceted uses that will improve industrial production, the environment and thus the quality of life on the planet.