Nediljko Budisa

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Nediljko Budisa 2012

Nediljko "Ned" Budisa ( Croatian Nediljko Budiša ; born November 21, 1966 in Šibenik , Croatia ) is a Croatian biochemist and professor (Tier 1 Canada Research Chair) for synthetic biology at the University of Manitoba in Winnipeg , Canada .

As a pioneer in the field of Genetic Code Engineering and Chemical Synthetic Biology ( xenobiology he has his research on a wide range of applications in both) bioorganic and medicinal chemistry , structural biology and biophysics , as well as in molecular biotechnology and metabolic and biomaterial aligned -Engineering. He is the author of the only textbook in his research area "Engineering the genetic code: expanding the amino acid repertoire for the design of novel proteins".

academic career

Ned Budisa graduated from the Faculty of Science at the University of Zagreb in 1990 with a diploma as a high school teacher in chemistry and biology. In 1993 he graduated from the same faculty with a BS in Molecular Biology and an M.Sc. in biophysics . He defended his doctoral thesis (with the grade summa cum laude ) in 1997 at the Technical University of Munich with Professor Robert Huber as doctoral supervisor. In 2005 he completed his habilitation at the Technical University of Munich. He then got a position as Junior Group Leader ("Molecular Biotechnology") at the Max Planck Institute for Biochemistry in Munich. From 2007 to 2010 he was also a member of CIPS M in Munich. In 2008, Ned Budisa was offered a W3 professorship for biocatalysis at the TU Berlin , which he accepted in 2010. He held this position as a full professorship until September 2018, then part-time as a freelance professor, as he accepted the position of Tier 1 CRC in Chemical Synthetic Biology at the University of Manitoba in October 2018. Ned Budisa is also a member of the Cluster of Excellence “Unifying Systems in Catalysis” (UniSysCat). He also founded the first Berlin iGEM team in 2014 .

research

Ned Budisa used the selective pressure incorporation method to incorporate single or multiple synthetic (i.e., non-canonical) amino acid analogs into proteins in vivo , preferably by sense codon reassignment. His method enables precise manipulation of the amino acid side chains, predominantly with analogues of the canonical amino acids proline , tryptophan and methionine . These attempts are often accompanied by simple metabolic engineering. The aim is to transfer bioorthogonal physico-chemical properties and reactions (e.g. chemoselective linkages such as click chemistry ) as well as spectroscopic features (e.g. blue or golden fluorescence or vibration energy transfer ) into the chemistry of life. In this way, the metabolism of living cells is enriched with elements that are rarely present in the metabolism (e.g. fluorine , selenium or tellurium ).

Ned Budisa is known for establishing the use of selenium-containing non-canonical amino acids for protein X-ray structure analysis and fluorine-containing analogues for 19 F-NMR spectroscopy and protein folding studies. He was the first to show that genetic code engineering can serve as a useful tool for the creation of therapeutic proteins and ribosomally synthesized peptide drugs. In addition, he succeeded in the innovative development of photoactivatable mussel-based underwater adhesives (as protein-based biomaterials). His fundamental contributions include the design of a chemical model that explains the role of methionine oxidation in prion-protein aggregation. Finally, he discovered the role of the proline side chain conformations ( endo-exo isomerism ) in protein folding and in protein stability and translation .

Together with his colleague Vladimir Kubyshkin, the hydrophobic artificial polyproline II helix was designed. The results from this project together with Budisa's earlier work on bioexpression using proline analogs contributed to the postulation of the alanine world hypothesis . She explains why nature has chosen the genetic code with "only" 20 canonical amino acids for ribosomal protein synthesis .

In 2015, Ned Budisa's team successfully carried out a long-term evolution experiment with bacterial cultures, which culminated in the complete, proteome-wide substitution of all 20,899 tryptophan residues with thienopyrrole-alanine in the genetic code of the bacterium Escherichia coli . This lays a solid basis for the evolution of life with alternative building blocks and alternative biochemistry. At the same time, this process offers an interesting route to a new biosecurity technology that separates synthetic cells from the natural environment with a "genetic firewall" ( biocontainment ). Similar experiments were carried out in collaboration with Beate Koksch (from the Free University of Berlin ) with fluorinated tryptophan analogs as xenobiotic compounds . During the adaptive evolution in the laboratory, an extraordinary physiological plasticity was discovered in microbial cultures, which makes them potential environmentally friendly tools for new bioremediation strategies.

Ned Budisa is actively involved in the debate about the possible social, ethical and philosophical effects of radical engineering of the genetic code in the context of synthetic cells and synthetic life with artificial biodiversity.

Awards (selection)

  • 2004: BioFuture Award
  • 2017: Fluorochemistry Publication Prize

Web links

Individual evidence

  1. ↑ Prof. Dr. Nediljko Budisa. Personal. Technical University of Berlin, accessed on January 22, 2020 .
  2. ↑ Dr. Ned Budisa. Profiles. University of Manitoba, accessed January 22, 2020 .
  3. ↑ Nediljko Budisa: Engineering the genetic code . Expanding the Amino Acid Repertoire for the Design of Novel Proteins. Wiley-VCH, Weinheim 2006, ISBN 3-527-31243-9 ( limited preview in the Google book search).
  4. ↑ Max Planck Institute of Biochemistry: Nediljko Budisa, Curriculum vitae ( Memento from January 5, 2011 in the Internet Archive )
  5. ↑ List of CIPSM professors. Ludwig Maximilians University of Munich, accessed on January 22, 2020 .
  6. ^ Institute for Chemistry - Biocatalysis. Technical University of Berlin, accessed on January 22, 2020 .
  7. ↑ Welcome from Ned Budisa by the University of Manitoba. University of Manitoba, accessed January 22, 2020 .
  8. ↑ UniSysCatGroup Leaders. Prof. Dr. Nediljko Budisa. UniSysCat Berlin, accessed on January 22, 2020 .
  9. ↑ iGEM ​​Team Berlin. iGEM ​​Berlin, accessed on January 22, 2020 .
  10. ↑ Nediljko Budisa: Prolegomena to Future Experimental Efforts on Genetic Code Engineering by Expanding Its Amino Acid Repertoire . In: Angewandte Chemie International Edition . tape 43 , no. 47 , December 3, 2004, p. 6426 , doi : 10.1002 / anie.200300646 .
  11. ↑ Sandra Lepthien, Lars Merkel, Nediljko Budisa: In Vivo Double and Triple Labeling of Proteins Using Synthetic Amino Acids . In: Angewandte Chemie International Edition . tape 49 , no. 32 , July 26, 2010, p. 5446 , doi : 10.1002 / anie.20030064 .
  12. ↑ Nina Bohlke, Nediljko Budisa: Sense codon emancipation for proteome-wide incorporation of noncanonical amino acids: rare isoleucine codon AUA as a target for genetic code expansion . In: FEMS Microbiology Letters . tape 351 , no. 2 , February 2014, p. 133 , doi : 10.1111 / 1574-6968.12371 .
  13. ↑ Jan-Stefan Völler, Nediljko Budisa: Coupling genetic code expansion and metabolic engineering for synthetic cells . In: Current Opinion in Biotechnology . tape 48 , December 2017, p. 1 , doi : 10.1016 / j.copbio.2017.02.002 .
  14. ↑ Matthias P. Exner, Tilmann Kuenzl, Tuyet Mai T. To, Zhaofei Ouyang, Sergej Schwagerus, Michael G. Hoesl, Christian PR Hackenberger, Marga C. Lensen, Sven Panke, Nediljko Budisa: Design of -Allylcysteine ​​in Situ Production and Incorporation Based on a novel Pyrrolysyl-tRNA Synthetase Variant . In: ChemBioChem . tape 18 , no. 1 , January 3, 2017, p. 85 , doi : 10.1002 / cbic.201600537 .
  15. ↑ S. Lepthien, MG Hoesl, L. Merkel, N. Budisa: Azatryptophans endow proteins with intrinsic blue fluorescence . In: Proceedings of the National Academy of Sciences . tape 105 , no. 42 , October 21, 2008, p. 16095 , doi : 10.1073 / pnas.0802804105 .
  16. ↑ Jae Hyun Bae, Marina Rubini, Gregor Jung, Georg Wiegand, Markus HJ Seifert, M.Kamran Azim, Jeong-Sun Kim, Andreas Zumbusch, Tad A. Holak, Luis Moroder, Robert Huber, Nediljko Budisa: Expansion of the Genetic Code Enables design of a novel “Gold” Class of Green Fluorescent Proteins . In: Journal of Molecular Biology . tape 328 , no. 5 , May 2003, pp. 1071 , doi : 10.1016 / S0022-2836 (03) 00364-4 ( deepdyve.com ).
  17. ↑ Tobias Baumann, Matthias Hauf, Fabian Schildhauer, Katharina B. Eberl, Patrick M. Durkin, Erhan Deniz, Jan G. Löffler, Carlos G. Acevedo-Rocha, Jelena Jaric, Berta M. Martins, Holger Dobbek, Jens Bredenbeck, Nediljko Budisa: Site-Resolved Observation of Vibrational Energy Transfer Using a Genetically Encoded Ultrafast Heater . In: Angewandte Chemie International Edition . tape 58 , no. 9 , February 25, 2019, p. 2899 , doi : 10.1002 / anie.201812995 .
  18. ↑ Federica Agostini, Jan-Stefan Völler, Beate Koksch, Carlos G. Acevedo-Rocha, Vladimir Kubyshkin, Nediljko Budisa: Biocatalysis with Unnatural Amino Acids: Enzymology Meets Xenobiology . In: Angewandte Chemie International Edition . tape 56 , no. 33 , August 7, 2017, p. 9680 , doi : 10.1002 / anie.201610129 .
  19. ↑ Nediljko Budisa, Boris Steipe, Pascal Demange, Christoph Eckerskorn, Josef Kellermann, Robert Huber: High-level Biosynthetic Substitution of Methionine in Proteins by its Analogs 2-Aminohexanoic Acid, Selenomethionine, Telluromethionine and Ethionine in Escherichia coli . In: European Journal of Biochemistry . tape 230 , no. 2 , June 1995, p. 788 , doi : 10.1111 / j.1432-1033.1995.0788h.x .
  20. ↑ Markus HJ Seifert, Dorota Ksiazek, M. Kamran Azim, Pawel Smialowski, Nediljko Budisa, Tad A. Holak: Slow Exchange in the Chromophore of a Green Fluorescent Protein Variant . In: Journal of the American Chemical Society . tape 124 , no. 27 , July 2002, p. 7932 , doi : 10.1021 / ja0257725 .
  21. ↑ N. Budisa, C. Minks, FJ Medrano, J. Lutz, R. Huber, L. Moroder: Residue-specific bioincorporation of non-natural, biologically active amino acids into proteins as possible drug carriers: Structure and stability of the per -thiaproline mutant of annexin V . In: Proceedings of the National Academy of Sciences . tape 95 , no. 2 , January 20, 1998, p. 455 , doi : 10.1073 / pnas.95.2.455 ( pnas.org ).
  22. ↑ Nediljko Budisa: Expanded genetic code for the engineering of ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) . In: Current Opinion in Biotechnology . tape 24 , no. 4 , August 2013, p. 591 , doi : 10.1016 / j.copbio.2013.02.026 .
  23. ↑ Matthias Hauf, Florian Richter, Tobias Schneider, Thomas Faidt, Berta M. Martins, Tobias Baumann, Patrick Durkin, Holger Dobbek, Karin Jacobs, Andreas Possible, Nediljko Budisa: Photoactivatable Mussel-Based Underwater Adhesive Proteins by an Expanded Genetic Code . In: ChemBioChem . tape 18 , no. 18 , 19 September 2017, p. 1819 , doi : 10.1002 / cbic.201700327 .
  24. ↑ C. Wolschner, A. Giese, HA Kretzschmar, R. Huber, L. Moroder, N. Budisa: Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein . In: Proceedings of the National Academy of Sciences . tape 106 , no. 19 , May 12, 2009, pp. 7756 , doi : 10.1073 / pnas.0902688106 ( pnas.org [PDF]).
  25. ↑ Thomas Steiner, Petra Hess, Jae Hyun Bae, Birgit Wiltschi, Luis Moroder, Nediljko Budisa, Wenqing Xu: Synthetic Biology of Proteins: Tuning GFPs Folding and Stability with Fluoroproline . In: PLoS ONE . tape 3 , no. 2 , February 27, 2008, p. e1680 , doi : 10.1371 / journal.pone.0001680 .
  26. ↑ Lili K. Doerfel, Ingo Wohlgemuth, Vladimir Kubyshkin, Agata L. Starosta, Daniel N. Wilson, Nediljko Budisa, Marina V. Rodnina: Entropic Contribution of Elongation Factor P to Proline Positioning at the Catalytic Center of the Ribosome . In: Journal of the American Chemical Society . tape 137 , no. 40 , September 29, 2015, p. 12997 , doi : 10.1021 / jacs.5b07427 .
  27. ↑ Vladimir Kubyshkin, Stephan L. Grage, Jochen Bürck, Anne S. Ulrich, Nediljko Budisa: Transmembrane Polyproline Helix . In: The Journal of Physical Chemistry Letters . tape 9 , no. 9 , April 12, 2018, p. 2170 , doi : 10.1021 / acs.jpclett.8b00829 .
  28. ↑ Vladimir Kubyshkin, Nediljko Budisa: Anticipating alien cells with alternative genetic codes: away from the alanine world! In: Current Opinion in Biotechnology . tape 60 , December 2019, p. 242 , doi : 10.1016 / j.copbio.2019.05.006 .
  29. ↑ Vladimir Kubyshkin, Carlos G. Acevedo-Rocha, Nediljko Budisa: On universal coding events in protein biogenesis . In: Biosystems . tape 164 , February 2017, p. 16-25 , doi : 10.1016 / j.biosystems.2017.10.004 , PMID 29030023 .
  30. ↑ Vladimir Kubyshkin, Nediljko Budisa: The Alanine World Model for the Development of the Amino Acid Repertoire in Protein Biosynthesis . In: International Journal of Molecular Sciences . tape 20 , no. November 21 , 2019, p. 5507 , doi : 10.3390 / ijms20215507 .
  31. ↑ Michael Georg Hoesl, Stefan Oehm, Patrick Durkin, Elise Darmon, Lauri Peil, Hans-Rudolf Aerni, Juri Rappsilber, Jesse Rinehart, David Leach, Dieter Söll, Nediljko Budisa: Chemical Evolution of a Bacterial Proteome . In: Angewandte Chemie International Edition . tape 54 , no. 34 , August 17, 2015, p. 10030 , doi : 10.1002 / anie.201502868 .
  32. ↑ Vladimir Kubyshkin, Nediljko Budisa: Synthetic alienation of microbial organisms by using genetic code engineering: Why and how? In: Biotechnology Journal . tape 12 , no. 8 , August 2017, p. 1600097 , doi : 10.1002 / biot.201600097 .
  33. ↑ Christian Diwo, Nediljko Budisa: Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust biocontainment system in Genetic isolation . In: Genes . tape 10 , no. 1 , January 2019, p. 17 , doi : 10.3390 / genes10010017 .
  34. ^ Carlos G. Acevedo-Rocha, Nediljko Budisa: On the Road towards Chemically Modified Organisms Endowed with a Genetic Firewall . In: Angewandte Chemie International Edition . tape 50 , no. 31 , July 25, 2011, p. 6960 , doi : 10.1002 / anie.201103010 .
  35. ↑ Federica Agostini, Ludwig Sinn, Daniel Petras, Christian J. Schipp, Vladimir Kubyshkin, Allison Ann Berger, Pieter C. Dorrestein, Juri Rappsilber, Nediljko Budisa, Beate Koksch: Laboratory evolution of Escherichia coli enables life based on fluorinated amino acids . In: BioRxiv . 2019, doi : 10.1101 / 665950 .
  36. ↑ Markus Schmidt, Lei Pei, Nediljko Budisa: Xenobiology: State-of-the-art, Ethics and Philosophy of new-to-nature organisms . In: Advances in Biochemical Engineering / Biotechnology . tape 162 , 2018, ISSN  0724-6145 , p. 301-315 , doi : 10.1007 / 10_2016_14 .
  37. ↑ BioFuture Award profile ( Memento from June 30, 2007 in the Internet Archive )
  38. ↑ UniCat - Fluorochemistry Publication Prize. Technical University of Berlin, accessed on January 22, 2020 .
personal data
SURNAME Budisa, Nediljko
ALTERNATIVE NAMES Budisa, Ned
BRIEF DESCRIPTION Croatian chemist and professor for biocatalysis at the TU Berlin
DATE OF BIRTH November 21, 1966
PLACE OF BIRTH Šibenik , Croatia