The evolution of the field of biosynthesis from the unravelling of the mode
of formation of natural products to the use of such knowledge to create ne
w compounds is reviewed using examples from the author's laboratory. The di
scussion focuses on the mode of operation of type II (spore pigment PKS) an
d type I (rifamycin PKS) polyketide synthases and their diversion to genera
te unnatural products, and on the genetics and biochemistry of deoxysugar f
ormation in granaticin biosynthesis as a prerequisite to combinatorial enzy
matic synthesis of unusual glycosides.