Biochemie II

Research

In the focus of our research are enzymes, which are elaborate proteins that catalyse cellular reactions with high specificity and efficiency.

Model system

Our preferred model system is the (βα)₈-barrel family of enzymes, which is the most frequently encountered protein fold. (βα)₈-barrel enzymes catalyse a large variety of mechanistically diverse reactions. The fold of the canonical (βα)₈-barrel consists of a central barrel of eight parallel β-strands, which are surrounded by eight external α-helices. Connecting loops are located at both the N-terminal (α-β loops) and the C-terminal (β-α loops) face of the barrel. Due to the spatial separation of structural elements that are important for stability and catalytic activity, (βα)₈-barrels provide an ideal scaffold for the study of enzyme evolution and the design of new enzymatic activities.

Projects

We are using rational design and directed evolution to engineer the stability and catalytic activity of enzymes, experimentally reconstruct the natural evolution of enzymes, assign functions to uncharacterised enzymes, and characterize allosteric interactions within multi-enzyme complexes. To this end, we apply a broad range of experimental and computational methods.

Team-Leaders

Chair:
Prof. Dr. Rein- hard Sterner

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Prof. Dr. Rainer Merkl

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Dr. Patrick Babinger

Alumni

Dr. Steffen Schmidt	1998-1999	MPI für Entwicklungsbiologie Tübingen	x
Dr. Silke Beissmann- Driemeier	Jan 1998 - Jan 2001	Ortlieb Vegetables & Nuts GmbH Bensheim	EMail
Vera Röhlich	Juli 2000 - Juni 2001	Weleda AG	EMail
Dr. Martina Henn-Sax	Sept 1998 - Dez 2001	abiturlernen.de	EMail
Dr. Andreas Ivens	Jan 2000 - Juni 2002	Baxter AG Wien	EMail
Dr. Stefan Hettwer	Apr 1998 - Sept 2002	Neurotune AG Schlieren, Schweiz	x
Dr. Satoshi Akanuma	Juli 2001 - Feb 2003	University of Pharmacy and Life Sciences, Tokyo	EMail
Jeannine Mohrlüder	März 2002 - März 2003	Universität Düsseldorf INB-2 Forschungszentrum Jülich	EMail
Dr. Birte Höcker	Nov 1998 - Juni 2003	MPI für Entwicklungsbiologie Tübingen	EMail
Dr. Manal Bosnali	Okt 2002 - März 2004	LIFE & BRAIN GmbH, Bonn	EMail
Natalie Heuer	Okt 2002 - März 2004	Universität Köln Institut für Biochemie	EMail
Simona Jansen	Juli 2000 - April 2004	Universität Köln Institut für Biochemie	EMail
Iris Lambeck	Dez 2003 - Dez 2004	Roche Pharma Basel QA Manager	EMail
Dr. Catharina Dönges	März 2000 - Jan 2005	Noeh Johannes Dönges 24-h Service	EMail
Susanne Marquardt	April 2004 - März 2005	Geneart AG, Regensburg	EMail
Birgit Schwarz	Dez 2003 - April 2005	Abbott Diagnostics Wiesbaden	EMail
Dr. Michaela Häger	Feb 2001 - Juni 2005	Preglem / Gedeon Richter, Köln und Hochschule Bonn-Rhein-Sieg	EMail
Dr. Karin Babinger	Juni 2005 - Okt 2005	Universität Regensburg Lehrstuhl für Anatomie I	EMail
Dr. Sonja Leopoldseder	2001 - Jan 2006	Profos AG, Regensburg	x
Christian Bolz	Jan 2006 - Nov 2006	ImevaX GmbH, München	x
Philipp Riede	Mai 2006 - Dez 2006	Oxford University student	EMail
Anne Schwabe	Dez 2006 - Juni 2007	University of Colorado grad student	x
Maximilian Plank	Juni 2006 - Aug 2007	University of Newcastle Australien, PhD student	x
Lorella Ungar	Jan 2004 - Aug 2007	FH Kempten Sekretariat	x
Sabine Einhell	Dez 2006 - Sept 2007	Universität Regensburg Studentin	EMail
Matthias Zwick	Sep 2006 - Dez 2007	Biozentrum Basel, Schweiz	x
Dr. Markus Richter	Mai 2004 - Aug 2008	Geneart AG, Regensburg	x
Dr. Jörg Claren	Nov 2004 - Dez 2008	Süd-Chemie AG, München	EMail
Ulrike Eßlinger	Juni 2008 - Mai 2009	Universität Regensburg, Klinik und Poliklinik für Innere Medizin II	x
Daniel Roderer	Sep 2008 - Aug 2009	ETH Zürick, Institut für Molekularbiologie und Biophysik	x
Bettina Sommer	Feb 2009 - Nov 2009	University of Prince Edward Island, Charlottetown, Canada	EMail
Dr. Felix List	Nov 2004 - März 2010	EMBL Hamburg	x
Dr. Alexander Ehrmann	Okt 2005 - Aug 2010	Bayer Schering Pharma AG	EMail
Dr. Tobias Seitz	April 2006 - Sept 2010	Roche Diagnostics GmbH (Pharma Biotech Penzberg)	EMail
Nadine Borst	Jan 2010 - Sept 2010	TU München, Lehrstuhl für biogene Rohstoffe (WZ Straubing)	EMail
Dr. Thomas Schwab	Jan 2006 - Dez 2010	Boehringer Ingelheim Pharma GmbH & Co KG, Biberach a.d.Riß	EMail
Dr. Susanne Dietrich	Okt 2005 - Dez 2010	Universitätsklinikum Regensburg AG Prof. Kerkhoff	EMail
Dr. Harald Guldan	Feb 2007 - Juni 2011	Lophius Biosciences GmbH Regensburg	x
Dr. Marco Bocola	Okt 20069 - Juli 2011	RWTH Aachen University Dept of Biotechnology	EMail
Dr. Hermann Zellner	April 2007 - Okt 2011	European Bioinformatics Institute EMBL - EBI Hinxton	x
Barbara Beer	Mai 2011 - Mai 2012	TU München (WZ Straubing) LS f. Chemie biogener Rohstoffe	x
Dr. Daniel Schneider	Dez 2006 - Mai 2012	Universität Konstanz, Lehrstuhl organische / zelluläre Chemie	x
Dr. Linn Carstensen	Okt 2008 - Juni 2012	Bayer Schering Pharma AG	EMail
Veronika Schmid	Jan 2012 - Sept 2012	Universitätsklinikum Regensburg AG Prof. Wagner	EMail
Bastian Groitl	Jan 2012 - Sept 2012	Universität Michigan, Ann Arbor Dept of Molecular, Cellular and Developmental Biology	EMail
Dr. Monika Meier	Feb 2008 - Jan 2013	Roche Diagnostics GmbH	EMail
Dr. Dietmar Birzer	März 2009 - Aug 2013	TNG Technology Consulting GmbH München	EMail
Dr. Josef Sperl	Aug 2009 - Aug 2013	TU München, Lehrstuhl für Chemie Biogener Rohstoffe (wiss.MA)	EMail
Dr. David Peterhoff	Aug 2009 - Okt 2013	Universitätsklinikum Regensburg Institut für Med. Mikrobiologie und Hygiene	EMail
Dr. Bernd Reisinger	Aug 2009 - Juli 2014	Physikalisch-Technische Bundesanstalt, Braunschweig	EMail
Dr. Florian Busch	Jan 2010 - Aug 2015	The Ohio State University, Columbus, USA	EMail

Publications

The following list summarizes all contributions of the scientific employees

2016 - 2015

Linde, M., Peterhoff, D., Sterner, R. & Babinger, P. (2016). Identification and characterization of heptaprenylglyceryl phosphate processing enzymes in Bacillus subtilis. J. Biol. Chem 291,14861-70.

Busch, F., Rajendran, C., Heyn, K., Schlee, S., Merkl, R. & Sterner, R. (2016). Ancestral tryptophan synthase reveals functional sophistication of primordial enzyme complexes. Cell Chem. Biol. 23, 709-715.

Plach, M. G., Reisinger, B., Sterner, R. & Merkl, R. (2016). Long-term persistence of bi-functionality contributes to the robustness of microbial life through exaptation. PLoS Genet. 12, e1005836.

Plach, M. G., Löffler, P., Merkl, R. & Sterner, R. (2015). Conversion of anthranilate synthase into isocorismate synthase: implications for the evolution of chorismate-utilizing enzymes. Angew. Chem. Int. Ed. Engl. 54, 11270-11274.

Ece S., Evran, S., Janda, J. O. Merkl, R. & Sterner, R. (2015). Improving thermal and detergent stability of Bacillus stearothermophilus neopullulanase by rational enzyme design. Protein Eng Des Sel 28, 147-151.

Woriedh, M., Merkl, R. & Dresselhaus, T. (2015). Maize EMBRYO SAC family peptides interact differentially with pollen tubes and fungal cells. J .Exp. Bot. 66, 5205-5216.

Filarsky, M., Zillner, K., Araya, I., Villar-Garea, A., Merkl, R., Längst, G. & Németh, A. (2015). The extended AT-hook is a novel RNA binding motif. RNA Biol. 12, 864-876.

Schneider, D., Kaiser, W., Stutz, C., Holinski, A., Mayans, O. & Babinger, P. (2015). YbiB from Escherichia coli, the defining member of the novel TrpD2 family of prokaryotic DNA-binding proteins. J .Biol.Chem. 290, 19527-19539.

2014 - 2013

Diermeier, S., Kolovos, P., Heizinger, L., Schwartz, U., Georgomanolis, T., Zirkel, A., Wedemann, G., Grosveld, F., Knoch, T. A., Merkl, R., Cook, P. R., Längst, G. & Papantonis, A. (2014). TNAα signalling primes chromatin for NF-_kB binding and induces rapid and widespread nucleosome repositioning. Genome Biol. 15, 536.

Hauptmann, J., Kater, L., Löffler, P., Merkl, R. & Meister, G. (2014). Generation of catalytic human Ago4 identifies structural elements important for RNA cleavage. RNA 20, 1532-1538.

Blaul, B., Steinbauer, R., Merkl. P., Merkl, R., Tschochner, H. & Ruther, J. (2014). Oleic acid is a precursor of linoleic acid and the male sex pheromone in Nasonia vitripennis. Insect. Biochem. Mol. Biol. 51, 33-40.

Janda, J. O., Popal, A., Bauer, J., Busch, M., Klocke, M., Spitzer, W., Keller, J. & Merkl, R. (2014). H2rs: deducing evolutionary and functionally important residue positions by means of an entropy and similarity based analysis of multiple sequence alignments. BMC Bioinformatics 15, 118.

Loedige, I., Stotz, M., Qamar, S., Kramer, K., Hennig, J., Schubert, T., Löffler, P., Merkl, R., Urlaub, H. & Meister, G. (2014). The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation. Genes Dev. 28, 749-764.

Busch, F., Rajendran, C., Mayans, O. Löffler, P., Merkl, R. & Sterner, R. (2014). TrpB2 Enzymes are O-Phospho-L-serine Dependent Tryptophan. Biochemistry 53, 6078-6083.

Peterhoff, D., Beer, B., Rajendran, C., Kumpula, E.P., Kapetaniou, E., Guldan, H., Wierenga, R.K., Sterner, R. & Babinger, P. (2014). A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization. Mol. Microbiol. 92, 885-899.

Sommer, B., Waege, I., Pöllmann, D., Seitz, T., Thomm, M., Sterner, R. & Hausner, W. (2014). Activation of a chimeric Rpb5/RpoH subunit using library selection. PLoS One 9, e87485.

Reisinger, B., Kuzmanovic, N., Löffler, P., Merkl, R., König, B. & Sterner, R. (2014). Expoiting protein symmetry to design light-controllable enzyme inhibitors. Angew. Chem. Int. Ed. 53, 595-598.

Reisinger, B., Sperl, J., Holinski, A., Schmid, V., Rajendran, C., Carstensen, L., Schlee, S., Blanquart, S., Merkl, R. & Sterner, R. (2014). Evidence for the existence of elaborate enzyme complexes in the paleoarchean era. J. Am. Chem. Soc. 136, 122-129.

Janda, J. O., Meier, A. & Merkl, R. (2013). CLIPS-4D: a classifier that distinguishes structurally and functionally important residue-positions based on sequence and 3D data. Bioinformatics 29, 3029-3035.

Sperl, J. M., Rohweder, B., Rajendran, C. & Sterner, R. (2013). Establishing catalytic activity on an artificial (βα)₈-barrel protein designed from identical half-barrels. FEBS Lett.. 587, 2798-2805.

Meier, M.M., Rajendran, C., Malisi, C., Fox, N.G., Xu, C., Schlee, S., Barondeau, D.P. Hoecker, B., Sterner, R. & Raushel, F.M. (2013). Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template. J. Am. Chem. Soc. 135, 11670-11677.

Hauptmann, J., Dueck, A., Harlander, S., Pfaff, J., Merkl, R. & Meister, G. (2013). Turning catalytically inactive human Argonaute proteins into active slicer enzymes. Nat. Struct. Mol. Biol. 20, 814-817.

Schlee, S., Dietrich, S., Kurcon, T., Delaney, P., Goodey, N.M. & Sterner, R. (2013). Kinetic mechanism of indole-3-glycerol phosphate synthase. Biochemistry 52, 132-142.

2012 - 2011

List, F., Vega, M. C., Razeto, A., Haeger, M. C., Sterner, R. & Wilmanns, M. (2012). Catalysis uncoupling in a glutamine amidotransferase bienzyme by unblocking the glutaminase active site. Chem. Biol. 19, 1589-1599.

Reisinger, B., Bocola, M., List, F., Claren, J., Rajendran, C. & Sterner, R. (2012). A sugar isomerization reaction established on various (βα)₈ -barrel scaffolds is based on substrate-assisted catalysis. Protein Eng. Des. Sel. 11, 751-760.

Carstensen, L., Sperl, J. M., Bocola, M., List, F., Schmid, F. X. & Sterner, R. (2012). Conservation of the folding mechanism between designed primordial (βα)₈-barrel proteins and their modern descendant. J. Am. Chem. Soc. 134, 12786-12791.

Dietrich, S., Borst, N., Schlee, S., Schneider, D., Janda, J. O., Sterner, R. & Merkl, R. (2012). Experimental assessment of the importance of amino acid positions identified by an entropy-based correlation analysis of multiple sequence alignments. Biochemistry 51, 5633-5641.

Peterhoff, D., Zellner, H., Gudan, H., Merkl, R., Sterner, R. & Babinger, P. (2012). Dimerization determines substrate specificity of a bacterial prenyltransferase. ChemBioChem 13, 1297-1303.

Evran, S., Telefoncu, A. & Sterner, R. (2012). Directed evolution of (βα)₈-barrel enzymes: establishing phosphoribosylanthranilate isomerisation activity on the scaffold of the tryptophan synthase α-subunit. Protein Eng. Des. Sel. 25, 285-293.

Craig, D. B., Schwab, T. & Sterner, R. (2012). Random mutagenesis suggests that sequence errors are not a major cause of variation in the activity of individual

molecules of β-galactosidase. Biochem. Cell Biol. 90, 540-547.

Carstensen, L., Zoldák, G., Schmid, F. X. & Sterner, R. (2012). Folding mechanism of an extremely thermostable (βα)₈-barrel enzyme: a high kinetic barrier protects the protein from denaturation. Biochemistry 51, 3420-3432.

List, F., Bocola, M., Haeger, M. C. & Sterner, R. (2012). Constitutively active glutaminase variants provide insights into the activation mechanism of anthranilate synthase. Biochemistry 51, 2812-2818.

Guldan, H., Matysik, F. M., Bocola, M., Sterner, R. & Babinger, P. (2011). Functional assignment of an enzyme that catalyzes the synthesis of an archaea-type ether lipid in bacteria. Angew. Chem. Int. Ed. Engl. 50, 8188-8191.

Fischer, A., Seitz, T., Lochner, A., Sterner, R., Merkl, R. & Bocola, M. (2011). A fast and precise approach for computational saturation mutagenesis and its experimental validation by using an artificial (βα)₈-barrel protein. ChemBioChem 12, 1544-1550.

Schwab, T. & Sterner, R. (2011). Stabilization of a metabolic enzyme by library selection in Thermus thermophilus. ChemBioChem 12, 1581-1588.

2010 - 2009

Ehrmann, A., Richter, K., Busch, F., Reimann, J., Albers, S.V. & Sterner, R. (2010). Ligand-inducted formation of a transient tryptophan synthase complex with αββ subunit stoichiometry. Biochemistry 49, 10842-10853.

B Mandach, C. & Merkl R. (2010) Genes optimized by evolution for accurate and fast translation encode in Archaea and Bacteria a braod and characteristic spectrum of protein functions. MC Genomics 11, 617.

Seitz, T., Thoma, R., Schoch, G.A., Stihle, M., Benz, J., D'Arcy, B., Wiget, A., Ruf, A., Hennig, M. & Sterner, R. (2010). Enhancing the stability and solubility of the glucocorticoid receptor ligand-binding domain by high-throughput library screening. J. Mol. Biol. 403, 562-577.

Liebold, C., List, F., Kalbitzer, H.R., Sterner, R. & Brunner, E. (2010). The interaction of ammonia and xenon with the imidazole glycerol phosphate synthase from Thermotoga maritima as detected by NMR spectroscopy. Protein Sci. 19, 1774-1782.

Richter, M., Bosnali, M., Carstensen, L., Seitz, T., Durchschlag, H., Blanquart, S., Merkl, R. & Sterner, R. (2010). Computational and experimental evidence for the evolution of a (βα)₈-barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds. J. Mol. Biol. 398, 763-773.

Drzewiecki, K., Angelov, A., Ballschmiter, M. Tiefenbach, K.-J., Sterner, R. & Liebl, W. (2010) Hyperthermostable acetyl xylan esterase. Microbial Biotechnol. 3, 84-92.

Merkl R, Wiezer A. (2009) GO4genome: A prokaryotic phylogeny based on genome organization. J. Mol. Evol. 68, 550-562.

Schlee, S., Deuss, M., Bruning, M., Ivens, A., Schwab, T., Hellmann, N., Mayans, O. & Sterner, R. (2009). Activation of anthranilate phosphoribosyl transferase from Sulfolobus solfataricus by removal of Mg-inhibition and acceleration of product release. Biochemistry 48, 5199-5209.

Claren, J., Malisi, C., Höcker, B. & Sterner, R. (2009). Establishing wild-type levels of catalytic activity on natural and artificial (βα)₈-barrel protein scaffolds. Proc. Natl. Acad. Sci. USA 106, 3704-3709.

Xiang, D. F., Kolb, P., Meier, M. M., Fedorov, E. V., Fedorov, A. A., Sterner, R., Almo S. C., Shoichet, B. K. & Raushel, F. M. (2009). Functional annotation and three-dimensional structure of Dr0930 from Deinococcus radiodurans: A close relative of phosphotriesterase in the amidohydrolase family. Biochemistry 48, 2237-2247.

Fischer, A., Enkler, N., Neudert, G., Bocola, M., Sterner, R. & Merkl, R. (2009). TransCent: Computational enzyme design by transferring active sites and considering constraints relevant for catalysis. BMC Bioinformatics 10, 54.

Höcker, B., Lochner, A., Seitz, T., Claren, J. & Sterner, R. (2009). High-resolution crystal structure of an artificial (βα)₈-barrel protein designed from identical half-barrels. Biochemistry 48, 1145-1147.

2008 - 2006

Guldan, H., Sterner, R. & Babinger, P. (2008). Identification and Characterization of a Bacterial Glycerol-1-phosphate Dehydrogenase: Ni²⁺ -Dependent AraM from Bacillus subtilis. Biochemistry 47, 7376-7384.

Merkl, R. & Zwick, M. (2008). H2r:Identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments. BMC Bioinformatics 9, 151.

Reetz, M. T., Rentzsch, M., Pletsch, A., Taglieber, A., Hollmann, F., Mondière, R. J. G., Dickmann, N., Höcker, B., Cerrone, S., Haeger, M. C. & Sterner, R. (2008). A Robust Protein Host for Anchoring Chelating Ligands and Organocatalysts. ChemBioChem 9, 552-564.

Schwab, T., Skegro, D., Mayans, O. & Sterner, R. (2008). A rationally designed monomeric variant of anthranilate phosphoribosyltransferase from Sulfolobus solfataricus is as active as the dimeric wild-type enzyme but less thermostable. J. Mol. Biol. 376, 506-516.

Seitz, T., Bocola, M., Claren, J. & Sterner, R. (2007). Stabilization of a (βα)₈-Barrel Protein Designed from Identical Half Barrels. J. Mol. Biol. 372, 114-129.

Merkl, R. (2007). Modelling the evolution of the archeal tryptophan synthase. BMC Evol Biol. 7, 59.

Merkl, R. (2006). AMIGOS: a method for the inspection of genomic organisation or structure and its application to characterise conserved gene arrangements. In Silico Biol. 6, 281-306.

Waack, S., Keller, O., Asper, R., Brodag, T., Damm, C., Fricke, W. F., Surovcik, K., Meinicke, P. & Merkl, R. (2006). Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models. BMC Bioinformatics 7, 142.

Merkl, R. (2006). A comparative categorization of protein function encoded in bacterial or archeal genomic islands. J Mol Evol. 62, 1-14.

Leopoldseder, S., Hettwer, S. & Sterner, R. (2006). Evolution of Multi-Enzyme Complexes: The Case of Tryptophan Synthase. Biochemistry 45, 14111-14119.

Marino, M., Deuss, M., Svergun, D., Konarev, P., Sterner, R. & Mayans, O. (2006). Structural and Mutational Analysis of Substrate Complexation by Anthranilate Phosphoribosyltransferase from Sulfolobus solfataricus. J. Biol. Chem. 281, 21410-21421.

2005 - 2003

Schneider, B., Knöchel, T., Darimont, B., Hennig, M., Dietrich, S., Babinger, K., Kirschner, K. & Sterner, R. (2005). Role of the N-terminal Extension of the (βα)₈-Barrel Enzyme Indole-3-Glycerol Phosphate Synthase for its Fold, Stability and Catalytic Activity. Biochemistry 44, 16405-16412.

Vega, C., Zou, P., Fernandez, F., Murphy, G., Sterner, R., Popov, A. & Wilmanns, M. (2005). Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA-synthetase-like subunit. Mol. Microbiol. 55, 675-686.

Wiezer, A. & Merkl, R. (2005). A comparative categorization of gene flux in diverse microbial species. Genomics 86, 462-475.

Höcker, B., Claren, J. & Sterner, R. (2004). Mimicking enzyme evolution by generating new (βα)₈-barrels from (βα)₄-half-barrels. Proc. Natl. Acad. Sci. USA 101, 16448-16453.

Thiemann, V., Dönges, C., Prowe, S., Sterner, R. & Antranikian, G. (2004). Characterisation of a thermoalkali-stable cyclodextrin glycosyltransferase from the anaerobic thermoalkaliphilic bacterium Anaerobranca gottschalkii. Arch. Microbiol. 182, 226-235.

Leopoldseder, S., Claren, J., Jürgens, C. & Sterner, R. (2004). Interconverting the catalytic activities of (βα)₈-barrel enzymes from different metabolic pathways: sequence requirements and molecular analysis. J. Mol. Biol. 337, 871-879.

Meinicke, P., Tech, M., Morgenstern, B. & Merkl, R. (2004). Oligo kernels for datamining on biological sequences: a case study on prokaryotic translation initiation sites. BMC Bioinformatics 5, 169.

Veith, B., Herzberg, C., Steckel, S., Feesche, J., Maurer, K. H., Ehrenreich, P., Bäumer, S., Henne, A., Liesegang, H., Merkl, R., Ehrenreich, A. & Gottschalk, G. (2004). The complete genome sequence of Bacillus licheniformis DSM13, an organism with great industrial potential. J Mol Microbiol Biotechnol. 7, 204-211.

Merkl, R. (2004). SIGI: score-based identification of genomic islands. BMC Bioinformatics 5, 22.

Henne, A., Brüggemann, H., Raasch, C., Wiezer, A., Hartsch, T., Liesegang, H., Johann, A., Lienard, T., Gohl, O., Martinez-Arias, R., Jacobi, C., Starkuviene, V., Schlenczeck, S., Dencker, S., Huber, R., Klenk, H. P., Kramer W., Merkl, R., Gottschalk, G., & Fritz, H.J.(2004). The genome sequence of the extreme thermophile Thermus thermophilus. Nat. Biotechnol. 22, 547-553.

Helmstaedt, K., Heinrich, G., Merkl, R. & Braus, G. H. (2004). Chorismate mutase of Thermus thermophilus is a monofunctional AroH class enzyme inhibited by tyrosine. Arch Microbiol. 181, 195-203.

Tech, M. & Merkl, R. (2003). YACOP: Enhanced gene prediction obtained by a combination of existing methods. In Silico Biol. 3, 441-451.

Merkl, R. (2003). A survey of codon and amino acid frequency bias in microbial genomes focusing on translational efficiency. J Mol Evol. 57, 453-466.

Wiezer, A. & Merkl, R. (2003). secureBLAST. In Silico Biol. 3, 405-409.

Bruggemann, H., Baumer, S., Fricke, W. F., Wiezer, A., Liesegang, H., Decker, I., Herzber, C., Martinez-Arias, R., Merkl, R., Henne, A. & Gottschalk, G. (2003). The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc Natl Acad Sci U S A 100, 1316-1321.

2002 - 2000

Henn-Sax, M., Thoma, R., Schmidt, S., Hennig, M., Kirschner, K. & Sterner, R. (2002). Two (βα)₈-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates. Biochemistry 41, 12032-12042.

Hettwer, S. & Sterner, R. (2002). A novel tryptophan synthase β-subunit from the hyperthermophile Thermotoga maritima: quaternary structure, steady-state kinetics, and putative physiological role. J. Biol. Chem. 277, 8194-8201.

Douangamath, A., Walker, M., Beismann-Driemeyer, S., Vega-Fernandez, M.C., Sterner, S. & Wilmanns, M. (2002). Structural evidence for ammonia tunnelling across the (βα)₈-barrel of the imidazole glycerol phosphate synthase bienzyme complex. Structure 10, 185-193.

Höcker, B., Schmidt, S. & Sterner, R. (2002). A common evolutionary origin of two elementary enzyme folds. FEBS letters 510, 133-135.

Larbig, K. D., Christmann, A., Johann, A., Klockgether, J., Hartsch, T., Merkl, R., Wiehlmann, L., Fritz, H. J. & Tümmler, B. (2002). Gene islands integrated into tRNA(Gly) genes confer genome diversity on a Pseudomonas aeruginosa clone. J Bacteriol. 184, 6665-6680.

Deppenmeier, U., Johann, A., Hartsch, T., Merkl, R., Schmitz, R. A., Martinez-Arias, R., Henne, A., Wiezer, A., Bäumer, S., Jacobi, C., Brüggemann, H., Lienard, T., Christmann, A., Bömeke, M., Steckel, S., Bhattacharyya, A., Lykidis, A., Overbeek, R., Klenk, H. P., Gunsalus, R. P., Fritz, H. J. & Gottschalk, G. (2002). The genome of Methanosarcina mazei: evidence for lateral gene transfer between bacteria and archaea. J Mol Microbiol Biotechnol. 4, 453-461.

Beismann-Driemeyer, S. & Sterner, R. (2001). Imidazole glycerol phosphate synthase from Thermotoga maritima: Quaternary structure, steady-state kinetics and reaction mechanism of the bi-enzyme complex. J. Biol. Chem. 276, 20387-20996.

Höcker, B., Beismann-Driemeyer, S., Hettwer, S., Lustig, A. & Sterner, R. (2001). Dissection of a (βα)₈-barrel enzyme into two folded halves. Nat. Struct. Biol. 8, 32-36.

Lang, D., Thoma, R., Henn-Sax, M., Sterner, R. & Wilmanns, M. (2000). Structural evidence for evolution of the β/α barrel scaffold by gene duplication and fusion. Science 289, 1546-1550.

Jürgens, C., Strom, A., Wegener, D., Hettwer, S., Wilmanns, M. & Sterner, R. (2000). Directed evolution of a (βα)₈-barrel enzyme to catalyze related reactions in two different metabolic pathways. Proc. Natl. Acad. Sci. USA 97, 9925-9930.

Thoma, R., Hennig, M., Sterner, R. & Kirschner, K. (2000). Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima. Structure 8, 265-276.

Reviews

Merkl, R. & Sterner, R. (2016). Ancestral protein reconstruction: techniques and applications. Biol. Chem. 397, 1-21.

List, F., Sterner, R. & Wilmanns, M. (2011). Related (βα)₈-barrel proteins in histidine and tryptophan biosynthesis: a paradigm to study enzyme evolution. ChemBioChem 12, 1487-1494.

Sterner, R. & Brunner, E. The relationship between catalytic activity, structural flexibility and conformational stability as deduced from the analysis of mesophilic - thermophilic enzyme pairs and protein engineering studies. In: F. Robb et al., eds., Thermophiles - Biology and Technology at High Temperatures, CRC Press, Boca Raton, London, New York, pp. 25-38, 2008.

Sterner, R. & Höcker, B. (2005). Catalytic versatility , stability, and evolution of the (βα)₈-barrel enzyme fold. Chemical Reviews 105, 4038-4055.

Jaenicke, R. & Sterner, R. Life at high temperatures. In: M. Dworkin et al., eds., The Procaryotes: An Evolving Electronic Resource for the Microbiological Community, 3rd edition (Latest update release 3.9, March 2002), New York, Springer-Verlag, 2000.

Sterner, R. & Liebl, W. (2001). Thermophilic Adaptation of Proteins. Crit. Rev. Biochem. Mol. Biol. 63, 39-106.

Sterner, R., Merz, A., Thoma, R. & Kirschner, K. (2001). Phosphoribosyl anthranilate isomerase and indoleglycerol phosphate synthase: tryptophan biosynthetic enzymes from Thermotoga maritima. Meth. Enzymol. 331, 270-280.

Sterner, R. (2001). 4Fe-4S ferredoxin from Thermotoga maritima. Meth. Enzymol. 334, 23-30.

Höcker, B., Jürgens, C., Wilmanns, M. & Sterner, R. (2001). Stability, catalytic versatility and evolution of the (βα)₈-barrel fold. Curr. Opin. Biotechnol. 12, 376-381.

Henn-Sax, M., Höcker, B., Wilmanns, M. & Sterner, R. (2001). Divergent evolution of (βα)₈-barrel enzymes. Biol. Chem. 382, 1315-1317.

Others

Meeting reports, books, book reviews, guest editorials

Merkl, R. (2015) Bioinformatik: Grundlagen, Algorithmen, Anwendungen. Wiley-VCH, Weinheim.

Sterner, R. (2011). Directed evolution: a powerful approach to optimising and understanding enzymes. ChemBioChem 12, 1439-1440.

Merkl, R. & Waack, Stephan (2009) Bioinformatik Interaktiv: Algorithmen und Praxis. Wiley-Blackwell, Weinheim.

Sterner, R., Merkl, R. & Raushel, F.M. (2008). Computational Design of Enzymes. Chem. Biol. 5, 421-423.

Sterner, R. & Skerra, A. (2007). Design von Enzymen und anderen Proteinen: Einblicke aus Natur, Labor und Computersimulationen. Biospektrum 07, 814.

Sterner, R. & Schmid, F.X. (2004). De novo design of an enzyme. Science 304, 1916-1917.

Schmid, F.X. & Sterner, R. (2004). Protein Design. ChemBioChem 5, 143-144.

Jaenicke, R. & Sterner, R. (2003). Protein Design at the Crossroads of Biotechnology, Chemistry, Theory, and Evolution. Futura 18, 5-10.

Jaenicke, R. & Sterner, R. (2003). Protein Design at the Crossroads of Biotechnology, Chemistry, Theory, and Evolution. Angew. Chem. Int. Ed. 42, 140-142.

Sterner, R. (2003). Book Review: Directed Molecular Evolution of Proteins or How to Improve Enzymes for Biocatalysis. Edited by S. Brakmann and K. Johnsson. ChemBioChem 4, 119.