The squalestatins, novel inhibitors of squalene synthase produced by a species of phoma: III. Biosynthesis

Abstract

The biosynthetic origin of the carbon and oxygen atoms of the novel fungal secondary metabolite 1 was studied. Incorporation studies with single and multiple labelled I3C precursors indicated that the major portion of the molecule was derived from two polyketide chains made up of acetate units. One of the chains had benzoic acid (which can be derived from phenylalanine) as a starter unit. The remaining carbons were derived from a four-carbon unit related to succinate and from methionine. Studies with [l-13C,18O2]acetate and 18O2 indicated that five of the oxygens, including both of the heterocyclic oxygens, were derived from atmospheric oxygen. The oxygens at the two ester carbonyls were derived from acetate. © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.