Natural Products in Chemical Biology

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ALKALOIDS

SARAH E. O'CONNOR

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts

How nature synthesizes complex secondary metabolites, or natural products, can be studied only by working within the disciplines of both chemistry and biology. Alkaloids are a complex group of natural products with diverse mechanisms of biosynthesis. This chapter highlights the biosynthesis of four major classes of plant-derived alkaloids. Only plant alkaloids for which significant genetic information has been obtained were chosen for review. Isoquinoline alkaloid, terpenoid indole alkaloid, tropane alkaloid, and purine alkaloid biosynthesis are described here. The chapter is intended to provide an overview of the basic mechanism of biosynthesis for selected members of each pathway. Manipulation of these pathways by metabolic engineering is highlighted also.

Alkaloids are a highly diverse group of natural products related only by the presence of a basic nitrogen atom located at some position in the molecule. Even among biosynthetically related classes of alkaloids, the chemical structures are often highly divergent. Although some classes of natural products have a recognizable biochemical paradigm that is centrally applied throughout the pathway, for example, the “assembly line” logic of polyketide biosynthesis (1), the biosynthetic pathways of alkaloids are as diverse as the structures. It is difficult to predict the biochemistry of a given alkaloid based solely ...