Protein Biochemistry and Fermentation Technology

Em Prof M W Fowler Sheffield 222 2836 M.W.Fowler@sheffield.ac.uk

My research interests are primarily concerned with natural products of therapeutic interest, in particular those derived from plant cells which have an extremely diverse and versatile chemistry. In the past my research groups have developed technologies to grow plant cells in large scale cell culture for the synthesis of a number of non-proteinaceous natural products mainly aimed at anti-infective (anti-fungal) and anti-cancer targets, including the anti-cancer agent taxol. More recently my research interests have focused on two things, novel therapeutically important proteins, typically enzymes from plant cells, and plant cells as potential host systems for the production of therapeutically important proteins derived from other, particularly, human cells.

Plants synthesise an array of nucleic acid repair enzymes, e.g. DNA ligases and polymerases. Some of these are already known to have therapeutic potential in areas such as cancer. A project is underway with Prof D P Hornby and DSMZ, Braunschweig, Germany, to investigate further the presence of such enzymes in a range of plant cells and to address their structure and functionality with therapeutic applications in mind.

The production of monoclonal antibodies and other therapeutically important proteins is increasingly an issue as the need for such agents increases. While systems for synthesis using human cells are operational, they are not always ideal and are also expensive. The particular nature of the functional structure of such proteins limits the range of other hosts available. Plant cell systems offer a potentially important alternative. Studies are under development with Dr D J Gilmour to investigate the feasibility of using plant cell systems as a host for functional and viable monoclonal synthesis.

Figure legend Needles from the Yew tree Taxus baccata which are a source of 10-deacetyl baccatin III (see below), a close relative of taxol, and which is synthetically modified by Bristol-Myers Squib to yield the potent anti-cancer agent Paclitaxel.

Figure Legend Schematic structure of 10-deacetyl baccatin III

Selected Publications Fowler, M.W. and Stafford, A.M. (1992) Plant cell culture, process systems and product synthesis. In: Plant Biotechnology, (eds. Fowler, M.W. and Warren, G.S.) Pergamon Pres, Oxford. pp79-98.

Fowler, M.W. (1992) Plant cell culture as a source of novel medicinal agents. In: New drugs from natural sources. (ed J. Coombes). IBC Technical Services, London. pp131-142.

Iqbal, M., Zafar, S.I., Stepan-Sarkissian, G. and Fowler, M.W. (1994) Indoor mass cultivation of red alga Porphyridium cruentum in different types of bioreactors.: effect of scale-up and vessel shape. J.Ferment. Technol. 75, 76-78.

Fowler, M.W. (1993) Plants, pharmaceuticals and plant cell culture: a perspective. In: Recontres Europeenes de Phytochemie. Actes du Colloque. (eds. Bruneton, J.and Guinaudeau) Angers France. pp124-133.

Fowler, M.W. (1994) The development of large scale process systems for the growth of plant cells. In: Better Living through Innovative Biochemical Engineering. (eds. Teo, W.K., Yap, M.G.S. and Oh, S.K.W.) National University of Singapore Press, Singapore, pp. 17-23.