Editorial

The present issue of PLANTA MEDICA is dedicated to the memory of Professor Dr. Ernst Reinhard (1926 - 2005), late Professor and Director of the Chair of Pharmaceutical Biology at the University of Tübingen, Germany. For many years (1978 - 1993), he served as Editor of Planta Medica and was widely recognized as a leading scientist in the field of plant biotechnology of medicinal plants.

The scientific work of Professor Reinhard focused on cell and tissue cultures of pharmaceutically valuable plants and their low molecular secondary constituents. Besides being of high scientific value, the investigations were always oriented towards putative industrial applications with the aim of broadening the technological potential of pharmaceutical biology. Early work dealt with the accumulation of various classes of compounds such as volatile oil in Ruta graveolens, or harman alkaloids in Peganum harmala [1], [2]. For these studies, investigations on qualitative and quantitative variations of phytohormones paralleled those analyzing the effect of light conditions [3].

The prime topics of Professor Reinhard’s scientific work were extensive studies on sterols and cardiac glycosides in cultures of Digitalis lanata and other Digitalis species. Suspension cultures, regenerated shoots or immobilized cells were used to investigate the potential of the systems [4]. Production of aglycones and their glycosides, uptake and biotransformation of various natural and partially synthetic derivatives, and cellular localization of substrates were investigated. Depending on the type of compound, glucosylation and acetylation in sugar chains as well as, in the case of β-methyldigitoxin, demethylation reactions were observed [4], [5], [6]. The 12β-hydroxylation leading from the digitoxin skeleton to the digoxin substitution pattern was one of the interesting and most intensely studied biotransformation reactions [7].

The various reactions described above were analyzed in different strains of the culture systems [4]. The finding that particular reactions in cell culture systems normally require optimal strain selection was very adequately described in the work of the Tübingen group [4].

When experimenting on cardiac glycoside metabolism in D. lanata cultures, the question of cellular accumulation and storage of products became essential. In this context, the group of Professor Reinhard remarkably contributed to improved isolation procedures for vacuoles and determination of accumulated glycosides [6], [8], [9]. As a result, differentiation between intermediates and end products could be clearly established. It should be emphasized that such knowledge is of importance if cell cultures are to be used on an economic scale [10].

Investigations involving various types of air-lift fermenters and bioreactors represented a very important part of the cell culture work of the Tübingen laboratory [11], [12], [13]. Biotransformation reactions of various cardenolide substrates were investigated in culture volumes between 12 and 300 litres [7], [14]. Questions regarding scale-up, growth periods, suitable growth media and adequate velocity of substrate addition had to be solved in order to establish good culture conditions [14]. It is remarkable that the relevant technical equipment was available in a university laboratory.

The successful and innovative research in the Tübingen Institute as well as related studies in several German and other laboratories worldwide formed the basis for an important and highly stimulatory international congress (”First International Congress on Medicinal Plant Research”) held in 1976 at the University of Munich. As co-organizer and speaker, Prof. Reinhard significantly contributed to the further development of the then emerging field of medicinal plant biotechnology [4]. The wide range of topics presented at this congress such as accumulation and biosynthesis of secondary plant constituents in cell and tissue cultures, genetic and regulatory aspects of plant cellular metabolism, bioreactor technology, degradative pathways of endogenous and exogenous aromatic compounds, and analytical methods for the selection of highly producing cell lines together outlined tracks for further developments. The congress turned out to be a milestone for the future successful growth of the cell and tissue culture field.

The Editors of this memorial issue express their sincere thanks to the authors of the scientific contributions. Former students and co-workers, colleagues and friends present recent achievements in the plant cell culture field and metabolic aspects of plant pharmaceuticals. Furthermore, they also report data on pharmaceutically interesting secondary compounds in fungal systems. Quite a few papers demonstrate that the focus of research has been increasingly put on genetic and molecular biological aspects of interesting compounds in plants and microorganisms in recent years. Thus, molecular biology on valuable plant products and analysis of regulatory parameters will form a rapidly expanding field in the years to come.

As a Planta Medica tradition, comprehensive reviews are also included in this issue. These reviews summarize the numerous publications in a particular field and place numerous pieces of information into a larger context. Thereby, single observations may trigger future considerations.

The Editors hope that the present issue will be viewed as a valuable contribution to the wide field of pharmaceutical biology and plant biotechnology. With Prof. Reinhard, we honour an outstanding scientist, a dear colleague and a faithful friend.

References

• 1 Reinhard E, Nagel M. The composition of the volatile oil of Ruta callus in relation to culture conditions and differentiation.  Nova Acta Leopold Supplementum. 1976;  7 335-43
• 2 Reinhard E, Corduan G, Volk O H. Detection of harmine in tissue cultures of Peganum harmala .  Phytochemistry. 1968;  7 503-4
• 3 Alfermann A W, Reinhard E. Influence of phytohormones on secondary product formation in plant cell cultures.  Nova Acta Leopold Supplementum. 1976;  7 345-56
• 4 Alfermann A W, Boy H M, Doeller P C, Hagedorn W, Heins M, Wahl J. et al .Biotranformation of cardiac glycosides by plant cell cultures. In: Barz W, Reinhard E, Zenk MH, editors Plant tissue culture and its biotechnological application. Berlin; Springer 1977: 125-41
• 5 Alfermann A W, Schuller I, Reinhard E. Biotransformation of cardiac glycosides by immobilized cells of Digitalis lanata .  Planta Med. 1980;  40 218-23
• 6 Kreis W, Hoelz H, Sutor R, Reinhard E. Cellular organization of cardenolide biotransformation in Digitalis grandiflora Mill.  Planta. 1993;  191 246-51
• 7 Kreis W, Reinhard E. 12β-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells: production of digoxin in 20-liter and 300-liter air-lift bioreactors.  J Biotechnol. 1992;  26 257-73
• 8 Hoelz H, Kreis W, Haug B, Reinhard E. Storage of cardiac glycosides in vacuoles of Digitalis lanata mesophyll cells.  Phytochemistry. 1993;  31 1167-71
• 9 Kreis W, Reinhard E. Rapid isolation of vacuoles from suspension-cultured Digitalis lanata cells.  J Plant Physiol. 1985;  121 385-90
• 10 Kreis W, Reinhard E. Selective uptake and vacuolar storage of primary cardiac glycosides by suspension-cultured Digitalis lanata cells.  J Plant Physiol. 1987;  128 311-26
• 11 Kreis W, Reinhard E. 12β-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells. Production of desacetyllanatoside C using a two stage culture method.  Planta Med. 1988;  54 143-8
• 12 Spieler H, Alfermann A W, Reinhard E. Biotransformation of β-methyldigitoxin by cell cultures of Digitalis lanata in airlift and stirred tank reactors.  Appl Microbiol Biotechnol. 1985;  23 1-4
• 13 Kreis W, Reinhard E. The production of secondary metabolites by plant cells cultivated in bioreactors.  Planta Med. 1989;  55 409-16
• 14 Kreis W, Reinhard E. Two-stage cultivation of Digitalis lanata cells: semicontinuous production of desacetyllanatoside C in 20-litre airlift bioreactors.  J Biotechnol. 1990;  16 123-35