Antibiotic biosynthesis: From natural to unnatural compounds

Abstract

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 new compounds is reviewed using examples from the author's laboratory. The discussion focuses on the mode of operation of type II (spore pigment PKS) and type I (rifamycin PKS) polyketide synthases and their diversion to generate unnatural products, and on the genetics and biochemistry of deoxysugar formation in granaticin biosynthesis as a prerequisite to combinatorial enzymatic synthesis of unusual glycosides.