Chemistry Reference
In-Depth Information
POLYKETIDE POLYETHERS
ALISON M. HILL
School of Biosciences, University of Exeter, Stocker Road, Exeter, United Kingdom
This review covers the biosynthesis of terrestrial and marine polyethers and discusses
their biologic properties and the molecular genetics and enzymology of the pro-
teins responsible for their formation. The biosynthesis of monensin, nanchangmycin,
nonactin, and the marine polyether ladders are discussed in detail. Novel enzymes
found only in type I polyketide polyether gene clusters that are responsible for the
epoxidation and cyclization of polyene biosynthetic intermediates are described. The
macrotetrolide biosynthetic gene cluster, which is an ACP-less type II polyketide
synthase that functions noniteratively is reviewed.
The first polyether antibiotic to be isolated was nigericin
1
in 1951. By 1983,
more than 70 terrestrial polyether antibiotics had been reported and Cane et al. (1)
had proposed a unified stereochemical model to account for their biosynthesis,
including the polyene-polyepoxide model of polyether formation. It took almost
20 years for the first polyether gene cluster to be reported (2). In contrast, the first
marine polyethers were reported in 1981, and a model to explain the biosynthesis
of marine polyether ladder compounds was proposed in 2006.
8.1 BIOLOGICAL BACKGROUND
Interest in these compounds (Fig. 8.1) derives from their ability to transport ions
across biologic membranes, and some terrestrial polyethers have been used widely
in veterinary medicine. Marine polyethers are responsible for numerous cases of
human food poisoning and toxic algal tides, which cause massive fish kills.
