Extraction of pharmacologically relevant triterpenes from plant cell cultures using the example of oleanolic and ursolic acid

(German title: Gewinnung von pharmakologisch relevanten Triterpenen aus pflanzlichen Zellkulturen am Beispiel von Oleanol- und Ursolsäure)

The substance group of triterpenes is increasingly becoming the focus of pharmaceutical research. The global market for active ingredients from plants totalled around US$ 30.7 billion in 2002, with the terpene substance class accounting for the dominant share and the highest growth rates. Triterpenes are generally isolated from various plant materials and, if necessary, chemically modified for pharmaceutical use. This procedure has several disadvantages. For example, the supply of raw materials is subject to strong fluctuations in quality and quantity, as the cultivation of medicinal plants is dependent on the weather. Chemical modification produces a large number of by-products that have to be laboriously separated from the target product. Some desirable modifications are difficult or impossible to obtain by chemical means.

This project therefore aims to investigate the extent to which triterpenes can be produced from sage in sufficient quality and quantity under reproducible conditions using plant cell cultures. The project will also investigate the modification of triterpenes by means of biotransformation with whole cell systems and with isolated enzymes. The project focusses on the two positional isomers oleanolic and ursolic acid, as these are among the most effective representatives of the triterpenes substance class. They have a variety of pharmacological effects and have been shown to have positive properties in terms of anti-inflammation, tumour control and hepatoprotection.

The aim is to establish an overall process that combines the steps of cultivation and product formation, as well as processing and biotransformation in a biotechnological mini plant. Based on the process data obtained, the overall process is to be modelled using the example of the fermentation of a sage cell line with subsequent esterification by Nocardia NRRL5646. With the help of the process model, the scale transfer of the individual process parameters and thus a corresponding up-scaling should be made possible. The increase in efficiency through the use of transgenic cell lines will be investigated in detail.

 

 

Partner

Prof. Dr. Thomas Bley (TU Dresden)

Prof. Dr. Ekkehard Neuhaus (TU Kaiserslautern)

StatusCompleted project
Funding organisationGerman Research Foundation
Funding period01/2010-12/2011
Funding codeUL 170/8-1

Publications and conference papers

  • K. Muffler, D. Leipold, M.-C. Scheller, C. Haas, J. Steingroewer, T. Bley, H. E. Neuhaus, M. A. Mirata, J. Schrader, R. Ulber; Biotransformation of triterpenes; Process Biochemistry (2010), doi:10.1016/j.procbio.2010.07.015
  • D. Leipold, G. Wünsch, K. Muffler, M. Schmidt, H.-J. Bart, H. Bergmann, E. Richling, R. Ulber; Synthesis of ursolic acid derivatives by microbial metabolism of ursolic acid with Nocardia sp. NRRL 5646; Process Biochemistry 45 (2010) 1043-1051
  • B. Ludwig, D. Geib, C. Haas, J. Steingroewerb, T. Bley, K. Muffler, R. Ulber; Whole-cell biotransformation of oleanolic acid by free and immobilized cells of Nocardia iowensis: Characterization of new metabolites; Eng. Life Sciences (2014) 10.1002/elsc.201400121
  • Scheller M-C, Muffler K, Leipold D, Möhlmann T, Neuhaus E, Steingroewer J, Haas C, Bley T, Ulber R; Biotransformation of ursolic acid from plant cells; New biotrends in green chemistry (2010) Dortmund
  • M.-C. Scheller, K. Muffler, G. Wünsch, D. Leipold, E. Neuhaus, T. Möhlmann,T. Bley, J. Steingroewer, C. Haas, R. Ulber; Gewinnung von Triterpenen aus Pflanzenzellkulturen; Jahrestagung der Biotechnologen & ProcessNet-Jahrestagung (2010) Aachen
  • K. Muffler, M.C. Scheller, B. Ludwig, D. Leipold, T. Möhlmann, E. Neuhaus, J. Steingroewer, C. Haas, T. Bley, R. Ulber; Production of biologically active triterpenes by biotransformation; European Congress of Chemical Engineering and Applied Biotechnology (2011) Berlin
  • C. Haas, S. Schulz, K. Muffler, T. Möhlmann, R. Ulber, E. Neuhaus, T. Bley, J. Steingroewer; Production of pharmaceutical relevant triterpenoids with plant in vitro cultures; European Congress of Chemical Engineering and Applied Biotechnology (2011) Berlin
  • S. Schulz, C. Haas, D. Leipold, K. Muffler, R. Ulber, A.I. Pavlov, T. Bley, J. Steingröwer; Screening methods for pharmaceutical relevant triterpenoids; European Congress of Chemical Engineering and Applied Biotechnology (2011) Berlin
  • S. Schulz, P. Kroll, C. Haas, R. Ulber, T. Bley, J. Steingroewer; Purification of Triterpenes from Salvia callus by sorption; GVC/DECHEMA Vortrags- und Diskussionstagung Biopharmazeutische Produktion (2012) Freiburg
  • B. Ludwig, K. Muffler, D. Leipold, T. Möhlmann, E. Neuhaus, J. Steingroewer, C. Haas, T. Bley, R. Ulber; Biotransformation von bioaktiven Triterpenen; GVC/DECHEMA Vortrags- und Diskussionstagung Biopharmazeutische Produktion (2012) Freiburg