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Ethylbenzene Dehydrogenase

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Molybdenum enzymes are distinguished by the presence of a unique active site containing molybdenum, one or two pteridine cofactors and additional ligands (i.e. amino acid residue of Ser, Cys, SeCys or Asp and very often oxygen Mo=O ligand)

 

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The main research topic is a study of ethylbenzene dehydrogenase (EBDH), the complex bacterial metalloenzyme
(abg 155 kDa) containing molybdenum cofactor  (MoCo), iron-sulfur clusters and heme b559 prosthetic group. EBDH catalyzes stereospecific hydroxylation of ethylbenzene to 1-(S)-phenylethanol. It also exhibits substrate promiscuity and as a result can be used in the synthesis of almost 50 different alkylaromatic and alkylheterocyclic secondary alcohols. 

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The research focuses both on fundamental studies of enzyme catalytic mechanism as well as on applied research aiming at the development of EBDH as biocatalyst for the synthesis of chiral alcohols. In JLBEC we formulated and validated by a combination of experimental and theoretical methods the mechanistic hypothesis for EBDH. We also developed immobilized EBDH as an efficient catalyst for the synthesis of chiral alcohols. 

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List of publication on the topic:

  1. J. Heider, M. Szaleniec, K. Sünwoldt , M. Boll, "Ethylbenzene Dehydrogenase and Related Molybdenum Enzymes Involved in Oxygen-Independent Alkyl Chain Hydroxylation", J. Mol. Microbiol. Biotechnol., 26 (2016) 45-62

  2. M. Szaleniec, A. Dudzik, B. Kozik, T. Borowski, J. Heider, M. Witko, "Mechanistic basis for the Enantioselectivity of the Anaerobic Hydroxylation of Alkylaromatic compounds by Ethylbenzene Dehydrogenase", J. Inorg. Biochem., 139 (2014) 9–20​

  3. M. Tataruch, J. Heider, J. Bryjak, P. Nowak, D. Knack, A.Czerniak, J. Liesiene, M. Szaleniec, "Suitability of the hydrocarbon-hydroxylating molybdenum-enzyme ethylbenzene dehydrogenase for industrial chiral alcohol production", J. Biotechnol., 192 (2014) 400-409

  4. D. H. Knack, J. L. Marshall, G. P. Harlow, A. Dudzik, M. Szaleniec, S-Y. Liu, J. Heider, "BN/CC isosteric compounds as new class of enzyme inhibitors: N- and B-ethyl-1,2-azaborine inhibit ethylbenzene hydroxylation as non-convertible substrate analogs", Angew. Chem. Int. Ed., 52 (2013) 2599 –2601

  5. A. Dudzik, B. Kozik, M. Tataruch, A. Wójcik, D. Knack, T. Borowski, J. Heider, M. Witko, M. Szaleniec, "The reaction mechanism of chiral hydroxylation of p-OH and p-NH2 substituted compounds by ethylbenzene dehydrogenase", Can. J. Chem., 91 (2013) 775-786

  6. M. Szaleniec, A. SalwiÅ„ski, T. Borowski, J. Heider, M. Witko, "Quantum chemical modeling studies of ethylbenzene dehydrogenase activity", Int. J. Quant. Chem., 112 (2012) 1990–1999

  7. M. Szaleniec, "Prediction of enzyme activity with neural network models based on electronic and geometrical features of substrates", Pharm. Reports, 64 (2012) 511-531

  8. D. Knack, C. Hagel, M. Szaleniec, A. Dudzik, A. Salwinski, J. Heider, "Substrate and inhibitor spectrum of ethylbenzene dehydrogenase: perspectives on application potential and catalytic mechanism", Appl. Environ. Microb., 78 (2012) 6475–6482

  9. M. Szaleniec, T. Borowski, K. Schühle, M. Witko, J. Heider, "Ab inito modeling of ethylbenzene dehydrogenase reaction mechanism", J. Am. Chem. Soc., 132 (2010) 6014-6024

  10. M.Szaleniec, R.Tadeusiewicz, M.Witko "The Selection of Optimal Neural Models for Forecasting of Biological Activity of Chemical Compounds", Neurocomputing, 72 (2008) 241-256

  11. M.Szaleniec, M.Witko, J.Heider "Quantum Chemical Modelling of the C-H Cleavage Mechanism in Oxidation of Ethylbenzene and Its Derivates by Ethylbenzene Dehydrogenase", J. Mol. Catal. A, 286 (2008) 128-136

  12. M. Szaleniec, C. Hagel, M. Menke, P. Nowak, M. Witko, J. Heider, "Kinetics and Mechanism of Oxygen-Independent Hydrocarbon Hydroxylation by Ethylbenzene Dehydrogenase", Biochemistry (US), 46 (2007) 7637-7646

  13. M. Szaleniec, M. Witko, R. Tadeusiewicz, J. Goclon "Application of Artificial Neural Networks and DFT-based Parameters for Prediction of Reaction Kinetics of Ethylbenzene Dehydrogenase", J. Comput.-Aided Molecular Design, 20 (2006)145-157

 

Patents

  • M. Szaleniec, M. Tataruch, J. Bryjak, P. Nowak, "Sposób otrzymywania chiralnie czystych alkoholi alkiloaromatycznych i alkiloheterocyklicznych oraz ukÅ‚ad reaktorowy do realizacji tego sposobu", Polish Patent PL406286

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scheme of Mo cofactor
reaction scheme depicting hydroxylation of ethylbenzne to S-1-phenylethanol
structure of ethylbenzene dehydrogease showing 3 subunits alpha, beta, gamma
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