The Biosynthesis of Aliphatic Polyketides

Abstract

Aliph. polyketides are a large family of natural products which exhibit an impressive range of biol. activities. They are synthesized by a common pathway in which units derived from acetate, propionate and butyrate are condensed onto a growing chain, which is initiated from a range of structurally varied carboxylic acid starter units, in a process closely resembling fatty acid biosynthesis. The intermediates remain bound to the polyketide synthase (PKS) throughout multiple rounds of chain extension, and to a variable degree, redn. of the newly formed β-keto functionality. It is the manner in which each different PKS controls the no. and type of extender units added, and the extent and stereochem. of redn. at each cycle which gives rise to the diverse structural variation seen in this family of natural products. Furthermore, the aglycon product of the PKS may be modified by post-PKS enzymes, including glycosidases, methyltransferases, acylases and oxidative enzymes, to produce still greater diversity. In this article the development of the field will be exemplified by a detailed discussion of the archetypal example of erythromycin A biosynthesis. This will then be followed by further discussion of other relevant areas of research in this field.