FP6 priority
1.1.3   Nanotechnologies and Nanosciences, Knowledge-based Multifunctional Materials and New Production Processes and Devices
Title of the proposal

Novel biocatalysts in synthesis and transformation of semisynthetic betalactam antibiotics

Slovak Academy of Sciences, Institute of Chemistry
Dubravska cesta 9, 842 38 Bratislava, Slovak Republic
+421 2 5941 0 211

Research subject for a potential FP6 project

Development of new advanced immobilized biocatalysts for environmentally friendly industrial production of pure, enantiomeric forms of essential intermediates for new generation of semisynthetic cephalosporins. As a starting point, an integrated, sequential system of two enzymatic reactions is considered, whereby the 1st enzyme being D-amino acid oxidase (D-AAO) and the 2nd one, glutaryl hydrolase (GH). Construction of two recombinant strains (E. coli) expressing oxidase and hydrolase will open perspectives for creation of strain producing both enzymes simultaneously.
Similarly, development of new advanced immobilized biocatalysts for environmentally friendly industrial pro- duction of pure, enantiomeric forms of essential intermediates for new generation of semisynthetic penicillins (and food additives) is proposed.
Analytical system for on-line monitoring of both analytes and catalytic activity of immobilized biocatalysts based on flow-injection system and integrating multiple excitation spectrofluorometry, amperometric sensors and flow microcalorimetry is proposed.

Recent international cooperation of the research team

INCO Copernicus Contract No No ERBIC15 CT 98 0809
Institute of Technologie and Biosystems Engineering, Federal Agriculture Research Centre (FAL),
D-381 16 Braunschweig, Prof. Klaus-Dieter Vorlop, Director (NSR)
Instituto de Catalisis Y Petrolequimica, Departamento de Biocatalisis, Conseco Superior de Investigationes Cientificas (CSIC), E-28049 Madrid, Dr. Jose M. Guisan (Spain)
Institute of Chemical Process Fundamentals, Academy of Sciences of the Czech Republic, CZ-165 02 Prague 6, Dr. Gabriela Kuncova, (Czech Republic)
Pure and Applied Biochemistry, Center for Chemistry and Chemical Engineering, Lund University, S-221 00 Lund, Prof. Bengt Danielsson (Sweden)
M.V. Lomonosov Moscow State University, Faculty of Chemistry, Dept Chemical Enzymology, RU-119899 Moscow, Prof. Vladimir I. Tishkov (Russia)

Proposerīs relevant publications related to the research subject

A. Vikartovska-Welwardova, E. Michalkova, P. Gemeiner: Enzyme flow microcalorimetry - A useful tool for screening of immobilized penicillin G acylase. J. Chem. Technol. Biotechnol. 73, 31-36 (1998)
A. Vikartovska-Welwardova, P. Gemeiner, V. Stefuca, P. Vrabel, E. Michalkova, L. Welward: Screning of immobilised Trigonopsis variabilis strains with cephalosporin C transforming activity by enzyme flow microcalorimetry. Biologia 53, 705-712 (1998)
V. Stefuca, P. Gemeiner: Investigation of catalytic properties of immobilized enzymes and cells by flow microcalorimetry. Advances in Biochemical Engineering{Biotechnology, Vol. 64 (T. Scheper, Ed.), pp. 71-99. Springer-Verlag, Berlin Heidelberg, 1999
L. Kurilova, P. Gemeiner, A. Vikartovska, H. Mikova, M. Rosenberg, M. Ilavsky: Calcium pectate gel beads for cell entrapment. 6. Morphology of stabilized and hardened calcium pectate gel beads with cells for immobilized biotechnology. J. Microencapsulation 17, 279-296 (2000)
M. Navratil, Z. Domeny, E. Sturdik, D. Smogrovicova, P. Gemeiner: Production of non-alcoholic beer using free and immobilized cells of Saccharomyces cerevisisae deficient in the tricarboxylic acid cycle. Biochem. Appl. Biotechnol. 35, 57-65 (2002)