Bioreactor engineering as an enabling technology to tap biodiversity. The case of taxol.
One barrier to exploiting the chemical and genetic diversity in nature is the difficulty of cultivating many organisms in a controlled manner. In some cases it is difficult to achieve growth. In many others, good growth is achieved, but the expression of the organism's genetic potential to make a desired product is not realized. The thesis of this paper is that a coupling of an understanding of reactor engineering principles with the basic knowledge of the biology is often necessary to circumvent these barriers. In many cases the construction of appropriate cultivation systems is a necessary step to better understanding of cellular physiology. In some cases the chemical of interest is of high social utility and comes from a natural source that is uncommon and difficult to secure. In these cases a method of controlled cultivation becomes a prerequisite for commercial exploitation. These points were illustrated using a taxol. Taxol is an important new anticancer drug whose development has been greatly impeded by supply problems. Taxol has been derived from the park of the pacific yew tree, a process that kills the tree. The pacific yew is a relatively uncommon tree and very slow growing. One alternative to the natural source is plant cell culture. Such cultures can produce significant levels of taxol with substantial release into the medium. Taxane products not observed in typical extracts from field-grown plants can be found in cell cultures, indicating the potential unmasking of pathways. These cultures are quite responsive to changes in their environments as illustrated by the summary of initial observations. With regard to natural compounds, biochemical engineers can play a major role in the capture and preservation of producing systems, in the discovery of useful compounds, and in providing the basis for commercial production of natural compounds.
Shuler
M L
ML
School of Chemical Engineering, Cornell University, Ithaca, New York 14853.
D001688:Biological Products; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D001952:Bridged-Ring Compounds; D002478:Cells, Cultured; D003247:Conservation of Natural Resources; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods*; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000302:isolation & purification; D059828:Plant Cells; D010944:Plants / Q000378:metabolism*; D043823:Taxoids; D014197:Trees
D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel