Natural Products via Enzymatic Reactions

Natural products are one of the major sources of today’s drugs. In addition, they provide intriguing insights into the taxonomy, evolution, biochemistry and social behavior of organisms, and their remarkable structural and biogenetic diversity and pharmacological properties are a rich inspiration for synthetic chemists.
Tradition- ally, natural productswere prepared in the laboratory by organic syntheticstrategies using small molecules as reagents. This situation has changed today, since enzymes are incorporated into many synthetic routes at the research and industrial scale. Enzymes possess several advantages over most classical reagents: they are nontox- ic, can be used at mild conditions and often exhibit exquisite stereo- and regios- electivity. These properties make them ideally suited to aid the construction of complex molecular scaffolds of natural products and their analogues. To fully exploit their potential, research at the interface of biochemistry, molecular genetics and organic synthesis is necessary. Biosynthetic studies uncover enzymatic cata- lysts with remarkable properties, such as fluorination “reagents”, Diels-Alderases and multimodular enzymes, where a single protein can catalyze dozens of individ- ual reactions. Molecular biologists develop novel methods by which enzymes can be improved in terms of substrate range, stability and turnover. In the field of synthesis, the concept of “total biosynthesis” has emerged, in which natural pro- ducts are generated in vitro using exclusively enzymes. Insights gained into enzy- matic structure and mechanism also heavily inspire scientists in organic catalysis and supramolecularchemistry to develop increasinglycomplex and efficient enzyme-like synthetic tools.