Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic subunits

Abstract

Recent advances in understanding of bacterial aromatic polyketide biosynthesis allow the development of a set of design rules for the rational manipulation of chain synthesis, reduction of keto groups and early cyclization steps by genetic engineering. The concept of rational design is illustrated by the preparation of Streptomyces strains that produce two new polyketides by expression of combinations of appropriate enzymatic subunits from naturally occurring polyketide synthases. The potential for generating molecular diversity within this class of molecules by genetic engineering is enormous.