Bioactive Agents from Natural Sources: Trends in Discovery and Application - Advances in Biochemical Engineering Biotechnology - page 126

synergistic use of biological and structural-directed natural product screening
approaches,natural product chemistry,and combinatorial strategies.

4.2.2
Biological Derivatization Methods

Since the early approaches on penicillin side chain modification [239-241],and
11 -hydroxylation of steroids [242, 243] which both mounted in important

industrial processes, the techniques of biological structure modification have
been further developed. Nowadays, a whole array of different methods using
microbial materials and processes is ready for the derivatization of bioactive
compounds.The various methods can be categorized into those employing the
native biosynthetic machinery ofa producing organism,those involving a mani-
pulation of the biosynthetic pathways on the enzymatic or genetic level, and
finally, the application of individual biosynthetic enzymes. The experimental
demands on the application ofthe various methods range from “simple”feeding
of biosynthetic precursors into standard cultivations to more sophisticated
approaches involving genetic engineering ofbiosynthetic enzymes.Genetics are
applied in the cell-based combination of biosynthetic genes from different
strains or the in vitro reconstitution of biosynthetic pathways with overexpres-
sed enzymes.A schematic overview of the different methods of biological deri-
vatization pointing to the experimental procedures, the necessary biological
material and the supply of precursors is provided in Fig.11.
All of the various methods of biological derivatization become possible due
to a relaxed substrate specificity of some of the biosynthetic enzymes,especial-

a

Fig. 11. Methods of biological derivatization