Use of 13C in biosynthetic studies. Incorporation of 13C-labeled acetate into chartreusin by Streptomyceschartreusis

Abstract

Examination by 13C nuclear magnetic resonance spectroscopy of chartreusin produced in cultures of Streptomyceschartreusis supplemented with [1-13C] and [2-13C]acetate showed that the 19-carbon aglycone component was derived entirely from acetate. In the spectrum of chartreusin enriched from [1,2-13C]acetate the signals for 16 of the carbon atoms were accompanied by satellites due to spin–spin coupling of intact 13C—13C units. The coupled pairs were matched with the aid of homonuclear single 13C-frequency decoupling. Of the uncoupled carbon atoms, two were derived from methyl groups of acetate and the third came from an acetate carboxyl group. The arrangement of paired and unpaired 13C atoms in chartreusin suggests that the aglycone is derived from a single 22-carbon polyketide chain. Cyclization to a benzpyrene-like intermediate followed by ring cleavage and loss of three carbon atoms provides a plausible route from the polyketide to the substituted isocoumarin structure of the aglycone.