(76a) Enzymatic Synthesis of Complex Natural Products

On account of their structural and biosynthetic complexity, most natural products have traditionally been discovered and produced from fermentable microorganisms. Within the past decade however, there has been an explosive growth of “orphan” biosynthetic pathways whose products are unknown. Many of these compounds cannot be accessed from their natural sources. In vitro reconstitution of these multi-enzyme systems has enabled efficient synthesis of relatively small quantities of some of these products for discovery applications. The benefits of scaling up these preparative methods are enormous, but significant challenges remain to be addressed. Using glycolipids and polyketides as examples, I will illustrate some of these opportunities and challenges.