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About us How to find us prof. dr. D.B. (Dick B) Janssen

prof. dr. D.B. Janssen

Professor in Chemical Biotechnology
prof. dr. D.B. Janssen
Telephone:
(Secretary):
E-mail:
d.b.janssen rug.nl

Curriculum vitae Prof. Dick B. Janssen

Overview

Present position
Full Professor Chemical Biotechnology
Groningen Biomolecular Sciences and Biotechnology Institute
University of Groningen, Nijenborgh 4, 9747 AG Groningen
The Netherlands. Tel: (31) 50-3634008, Fax: (31) 50-3634165.
E-mail: d.b.janssen rug.nl
Website: http://www.rug.nl/research/biotransformation-biocatalysis/    


Education and career

1993-now       Full Professor Chemical Biotechnology and chair unit Biotransformation and Biocatalysis, University of Groningen. Research program: biodegradation of xenobiotics, enzyme discovery and engineering for biocatalysis, transformation of synthetic compounds, computation-supported enzyme engineering.

1999-2004     Director of GBB (Groningen Biomolecular Sciences and Biotechnology Institute).

1992-1993     Associate professor at the University of Groningen. Research: genetics, biochemistry and engineering of bacterial dehalogenases.

1988-1993     Position as KNAW fellow researcher at the University of Groningen. Protein engineering of dehalogenases.

1988               Visiting scholar at the Stanford University, prof. Perry L. McCarty. Biodegra­dation of chlorinated solvents.

1982-1987     Post-doc at the University of Groningen, Department of Biochemistry, with Bernard Witholt. Research on bacterial degradation of chlorinated compounds, discovery of dehalogenases.

1977-1982     Ph.D. study at the Department of Microbiology, at the University of Nijmegen. Promotor Prof. Godfried D. Vogels, referent Dr. Chris van der Drift.

1971-1977     Study Chemistry (S2) at the University of Nijmegen. Specialization: biochemistry and chemical microbiology.

 

Teaching

BSc courses Bioenergy, Biocatalysis and Membrane Enzymology, Track Practical
MSc courses Protein Engineering, Biocatalysis and Green Chemistry

 

Research

The research of the Biotransformation and Biocatalysis group is aimed at obtaining insight in the enzymology of the microbial transformation of synthetic compounds, and the development of improved biocatalysts for such transformations. We study catalytic mechanisms, kinetic properties, and structure-function relationships in enzymes that can be used for regio- and enantioselective synthesis reactions for preparing fine chemicals. Obtaining new enzymes by enrichment, genome mining, and high-throughput screening as well as their improvement by structure-based protein engineering and directed evolution are important parts of this work. Computational approaches are increasingly used to improve enzyme stability and selectivity. Applications are developed in various programs with external partners.

 

Publications

Over 280 publications (refereed international scientific journals). Thomson-Reuters Web-of-Science: h-index = 63, over 12,000 citations. Google Scholar: h=79 over 20,500 citations.

 

Fellowships, awards and grants

Received over 40 different research grants, including:

  • BioTrans Senior Award 2019.
  • Host/supervisor for 2 CSC and 2 Conacyt fellowship holders
  • Two B-Basic grants, and four BE-Basic grants
  • Four EU FP4-6 grants, six different EU FP7 grants, 1 EU H2010 grant (ES-Cat)
  • Industrial awards: DSM Milieuprijs NL (1995, 2nd place; for research on the biodegra­dation of halogenated compounds), DSM Industrial Innovation Award (2004; for penicillin acylase engineering)
  • Industrial research grants from DSM, Monsanto, Ciba Fine Chemicals, BASF, EnzyPep BV
  • Research grants from NWO-STW (Metagenomics for Enzyme Discovery), NWO-Chemical Sciences (Halohydrin Dehalogenase Engineering), NWO-ACTS
  • Research grants from the Dutch innovation programs Environmental Biotechnology (Biodegradation of Xenobiotic Compounds), Biocatalysis (Epoxide Hydrolases), and Protein Engineering (Dehalogenases)
  • KNAW personal fellowship in 1998 (5-years).

 

Supervision and mentoring

The research group is currently composed of 1 technician, 6 PhD students (grant-funded), and 3 post docs (grant-funded). As PI Dick Janssen supervised or co-supervised the completion of over 48 PhD theses and the research of over 20 post-docs. Many former PhD students now hold important positions in academia or industry.

 

Selected invited lectures (recent)

I present at ca. 4-5 international conference or workshops annually. Examples:

  • Biotrans 2019, Groningen. BioTrans Senior Award lecture
  • VAAM 2019, Mainz, Germany. University of Bologna
  • EMBO workshop biocatalysis (Pavia 2018)
  • Gordon Conference Biocatalysis (2012, 2018)
  • Enzyme Engineering Conferences (Korea 2005, Harrison Hot Springs Canada 2007, Vail 1011, Florida 2015, Toulouse 2017)
  • ACS annual meeting (Philadelphia 2013, Washington DC 2017)
  • Summerschool Systems Biocatalysis, Certosa di Pontignano, Italy (2016)
  • Gordon conferences Microbiology, Environmental Sciences (2000-2013)
  • FEBS (Petersburg 2013) and FEMS (Maastricht 2015)
  • Industrial presentations (Degussa 2010, Merck Corp. 2013, BASF 2010, 2014, 2019, Enzypep 2015)
  • Biotrans conferences (Darmstadt 2011, La Grande Motte 1997)
  • Biocat Conferences (Hamburg, 2008, 2006)
  • Protein Engineering for Biocatalysis, Greifswald (2012)
  • Modeling and Design of Molecular Materials (MDMM Kudowa Zdroj, Poland, 2014)
  • CLIB-International-Conference (Dusseldorf, 2014)
  • Zing conference Biocatalysis (Mexico 2013)
  • 3rd EuCHeMS Chemistry Congress (Nuernberg, 2010).

 

 Other selected responsibilities

  • Reviewer for ISAB BioMedTech Graz (2019)
  • Convener 7th EuCheMS, Liverpool (2018)
  • Coordinator of EU-funded RTD projects "Epoxide hydrolases", and "Dehalogenases"
  • Conference chairs: Chair of the Enzyme Engineering Conference XX, 2009, Groningen, the Netherlands; Chair of International MicroB3-Metaexplore workshop, October 2013, Groningen, the Netherlands
  • Director of the Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen (1999-2004)
  • Member Org. Committee international conferences (e.g. EMBO conference Catalytic Mechanisms by Biological Systems, 2012, Groningen)
  • Member international ERA-IB review committee 2015-2016
  • Chairman Scientific Advisory Board Biotech-Genomik, Germany (2006-2010)
  • Chair or member of committees to evaluate and rank research proposals for the Dutch science foundation NWO (CW-Veni, CW-Echo, CW-Top, NWO-Vici, STW-Veni).

 

Scientific achievements

Vision

The vision of the group is that greening of the chemistry and energy sectors will be of utmost importance for the transition to a sustainable society in the 21st century, and that enzyme-based conversions employing new and robust enzymes have a key role to play in this transition. Furthermore, we envisage a slow and steady replacement of the current labor-intensive, costly and time-consuming laboratory research in biocatalyst development by computational approaches, wherever possible. The drastic redesign of enzymes for application in sustainable chemistry requires multiple mutations of which the cumulative effects on stability, active site structure and catalytic performance can only be estimated with innovative powerful computational enzyme design and ranking protocols.

The group originally worked on the discovery and engineering of enzymes relevant for the biodegradation of xenobiotic chemicals, and established a unique position by combining studies on biodegradability with structural biology and protein engineering. A variety of tools is used: classical microbiological enrichment with analysis of catabolic pathways; genome mining, using specific functional motifs for discovery of enzymes with specific catalytic profiles; and also environmental gene libraries, where high-throughput screening is used for mining genes for new enzymes from diverse environments, without isolation of specific cultures. Many new enzymes were characterized, cloned, and purified for structural studies. Based on the results, for the first time, biodegradability could be interpreted in the context of protein structures, catalytic mechanisms, and evolutionary events leading to new enzyme activities. Many labs use organisms, enzymes, clones, structures, and tools that we have developed for their own research. Other groups have chosen these systems for analysis by quantum mechanical calculations (T.C. Bruice, A. Warshel, J. Gao, A. Shurki, F. Himo). An overview and a few recent publications from our lab:

  • Palacio CM, Rozeboom HJ, Lanfranchi E, Meng Q, Otzen M, Janssen DB. 2019. Biochemical properties of a Pseudomonas aminotransferase involved in caprolactam FEBS  286: 4086–4102.
  • Atashgahi S, Liebensteiner MG, Janssen DB, Smidt H, Stams AJM, Sipkema D. 2018. Microbial synthesis and transformation of inorganic and organic chlorine compounds. Front Microbiol 9:3079.
  • Otzen M, Palacio C, Janssen DB. 2018. Characterization of the caprolactam degradation pathway in Pseudomonas jessenii using mass spectrometry-based proteomics. Appl Microbiol Biotechnol. 102:6699-6711.
  • Samin G, Pavlova M, Arif MI, Postema CP, Damborsky J, Janssen DB. 2014. A Pseudomonas putida strain genetically engineered for 1,2,3-trichloropropane bioremediation. Appl Environ Microbiol. 80:5467-76.
  • van Leeuwen JG, Wijma HJ, Floor RJ, van der Laan JM, Janssen DB. 2012. Directed evolution strategies for enantiocomplementary haloalkane dehalogenases: from chemical waste to enantiopure building blocks. ChemBiochem 13:137-48.
  • Janssen DB. Evolving haloalkane dehalogenases. 2004. Curr Opin Chem Biol 8:150-9.

Currently, the main topic of the group is enzyme discovery and protein engineering for biocatalysis.  The team investigated penicillin acylases for enzymatic preparation of semi-synthetic antibiotics, which led to enzymes with improved synthesis/hydrolysis ratios and industrial innovation with enzymatic routes for synthesis of semi-synthetic antibiotics by DSM. The also discovered the β-ammonia lyase activity of phenylalanine aminomutases, and used rational engineering of aminomutase to convert them into lyases with β-selectivity. Example papers:

  • Lanfranchi E, Trajković M, Barta K, de Vries JG, Janssen DB. 2019. Exploring the selective demethylation of aryl methyl ethers with a Pseudomonas rieske monooxygenase. ChemBiochem 20:118-125
  • Beyer N, Kulig JK, Fraaije MW, Hayes MA, Janssen DB. 2018. Exploring PTDH-P450BM3 variants for the synthesis of drug metabolites. ChemBiochem 19:326-337.
  • Nuijens T, Toplak A, Quaedflieg PJLM, Drenth J, Wu B, Janssen DB. 2016. Engineering a diverse ligase toolbox for peptide segment condensation. Adv Synth Catal 358: 4041-4048.
  • Toplak A, Nuijens T, Quaedflieg PJLM , Wu B, Janssen DB. 2016. Peptiligase, an anzyme for efficient chemoenzymatic peptide synthesis and cyclization in water. Adv Synth Catal 358: 2140-47.
  • Palacio CM, Crismaru CG, Bartsch S, Navickas V, Ditrich K, Breuer M, Abu R, Woodley JM, Baldenius K, Wu B, Janssen DB. 2016. Enzymatic network for production of ether amines from alcohols. Biotechnol Bioeng 113:1853-61.
  • Heberling MM, Masman MF, Bartsch S, Wybenga GG, Dijkstra BW, Marrink SJ, Janssen DB. 2015. Ironing out their differences: dissecting the structural determinants of a phenylalanine aminomutase and ammonia lyase. ACS Chem Biol 10:989-97.
  • Wu B, Szymanski W, Wybenga GG, Heberling MM, Bartsch S, de Wildeman S, Poelarends GJ, Feringa BL, Dijkstra BW, Janssen DB. 2012. Mechanism-inspired engineering of phenylalanine aminomutase for enhanced β-regioselective asymmetric amination of cinnamates. Angew Chem Int Ed Engl 51:482-6.

Since 2010, the group is working on the introduction of computational methods in biocatalyst engineering projects. This led, in collaboration with the group of D. Baker, Seattle, to the development of the FRESCO workflow (framework for enzyme stabilization by computational design) and the CASCO workflow (catalytic selectivity by computational design and screening) for protein engineering. We demonstrated the importance of High-Throughput Multiple Initialization Molecular Dynamics (HTMI-MD) for conformational sampling relevant for catalysis. The current proposal aims to make the next leap forward: engineering completely new reaction types and substrate selectivity in enzymes. Example papers:

  • Li R, Wijma HJ, Song L, Cui Y, Otzen M, Tian Y, Du J, Li T, Niu D, Chen Y, Feng J, Han J, Chen H, Tao Y, Janssen DB, Wu B. 2018. Computational redesign of enzymes for regio- and enantioselective hydroamination. Nat Chem Biol 14:664-670.
  • Arabnejad H, Dal Lago M, Jekel PA, Floor RJ, Thunnissen AW, Terwisscha van Scheltinga AC, Wijma HJ, Janssen DB. 2016. A robust cosolvent-compatible halohydrin dehalogenase by computational library design. Protein Eng Des Sel 30:173-187.
  • Wu B, Wijma HJ, Song L, Rozeboom HJ, Poloni C, Tian Y, Arif MI, Nuijens T, Quaedflieg PJLM, Szymanski W, Feringa BL, Janssen DB. 2016. Versatile peptide C-terminal functionalization via a computationally engineered peptide amidase. ACS Catal 6:5405-5414. Elected ACS paper-of-the-day.
  • Wijma HJ, Floor RF, Bjelic S, Marrink SJ, Baker D, Janssen DB. 2015. Enantioselective enzymes by computational design and in silico screening. Angew Chem Int Ed 54:3726-30.
  • Floor RJ, Wijma HJ, Colpa DI, Ramos-Silva A, Jekel PA, Szymanski W, Feringa BL, Marrink SJ, Janssen DB. 2014. Computational library design for increasing haloalkane dehalogenase stability. Chembiochem 15:1660-72. Selected on the journal website as a very important paper.
  • Floor RJ, Wijma HJ, Jekel PA, Terwisscha van Scheltinga AC, Dijkstra BW, Janssen DB. 2015. X-ray crystallographic validation of structure predictions used in computational design for protein stabilization. Proteins 83:940-51
  • Wijma HJ, Floor RJ, Jekel PA, Baker D, Marrink SJ, Janssen DB. 2014. Computationally designed libraries for rapid enzyme stabilization. Protein Eng Des Sel 27:49-58. Most-red paper of the journal 2016-2017.

The research program, especially the computational enzyme (re)design, makes intensive use of crystallographic and molecular dynamics expertise. Structures are used to design engineering workflows for molecular enzyme engineering and to interpret properties of novel and mutated enzymes. In house data collection allows rapid access and flexibility in university-industry collaborations.

  • Palacio CM, Rozeboom HJ, Lanfranchi E, Meng Q, Otzen M, Janssen DB. 2019. Biochemical properties of a Pseudomonas aminotransferase involved in caprolactam metabolism. FEBS J. 286:4086-4102.
  • Li R, Wijma HJ, Song L, Cui Y, Otzen M, Tian Y, Du J, Li T, Niu D, Chen Y, Feng J, Han J, Chen H, Tao Y, Janssen DB, Wu B. 2018. Computational redesign of enzymes for regio- and enantioselective hydroamination. Nat Chem Biol 14:664-670.
  • Schmidt M, Toplak A, Rozeboom HJ, Wijma HJ, Quaedflieg PJLM, van Maarseveen JH, Janssen DB, Nuijens T. 2018. Design of a substrate-tailored peptiligase variant for the efficient synthesis of thymosin-α-1. Org Biomol Chem 16:609-618.
  • Lee M, Rozeboom HJ, de Waal PP, de Jong RM, Dudek HM, Janssen DB. 2017. Metal dependence of the xylose isomerase from Piromyces E2 explored by activity profiling and protein crystallography. Biochemistry 56:5991-6005.
  • Floor RJ, Wijma HJ, Jekel PA, Terwisscha van Scheltinga AC, Dijkstra BW, Janssen DB. 2015. X-ray crystallographic validation of structure predictions used in computational design for protein stabilization. Proteins 83:940-51

 

Outreach and societal impact

The relevance of the work was summarized by the QANU Research Review Chemistry (2011): "The research conducted by the group has a high societal impact. The aim is to engineer enzymes that may have industrial applications. Most of the enzymes aim at a cleaner and greener production, and there are several examples of the results of the research that have been commercialized. The unique competences of the group are highly relevant in the education of PhD-students."

The group organizes International Masterclasses on the use of Computational Methods in Enzyme Engineering. Prominent scientists present lectures in computational approaches, and afternoons are used for hand-on computer training (visualization, disulfide bond design, docking, MD, design of stabilizing mutations). The April 2015 masterclass (30 students) was fully booked. It was repeated in 2019 and helps other groups and young scientists to adopt established computational tools in enzyme engineering. The group is open to sharing results, know-how and materials from its own projects. Scripts, protocols and clones are made available to other scientists.

The development of novel enzyme catalysts contributes to a sustainable society since biocatalysis can out-phase many polluting existing processes. The use of computational tools in enzyme engineering will boost the development of enzymatic steps for use in synthetic biology and white biotechnology, e.g. in enzymatic biomass processing. The group collaborates with key industrial players and academic groups on the application of enzyme stabilization protocols (FRESCO) that are essential for the introduction of new bioprocesses.

 

Partners

The research of the Biotransformation and Biocatalysis group is carried out in close collaboration with research groups from GBB (X-ray crystallography), the Stratingh Institute for Chemistry (Synthetic Organic Chemistry). Externally, we collaborate with industrial partners like DSM, BASF and EnzyPep and with various academic institutions through different EU projects.

 

Personal details

Full name:      Dirk Barend Janssen

Origin:            Heelsum, The Netherlands, July 24, 1954. Grew up on a farm called de Broekhorst on the slopes of de Noordberg, close to the river Rhine between Wageningen and Arnhem

Nationality:    Dutch

Residence:     Roden, Province of Drenthe, The Netherlands


Non-professional interests

  • Outdoors, hiking and climbing in remote places (Iceland, Galdhoppigen, Ortler, Mt. Blanc, Weisshorn, Chimborazo, Mt. Whitney, ..), cycling (Boersberg, Couberg, Stelvio, Trollstigen, ..)
  • Bee keeping
  • Travel, cities (Petersburg, Troyes, Bologna)
  • Societal: history, Bach, (inter)national politics
  • Scientific: evolution, origin of life, consciousness.

 

 

Last modified:31 October 2019 2.51 p.m.

Contact information

Groningen Biomolecular Sciences and Biotechnology Institute

Room:
5115.0119
Telephone:
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