Biosynthesis of Pyoluteorin: A Mixed Polyketide-Tricarboxylic Acid Cycle Origin Demonstrated by [l,2 -13C2]Acetate Incorporation

Pyoluteorin (1) is an antibiotic and phytotoxic metabolite of several Pseudomonas spp. [1 — 3]. Its biosynthesis had not been studied previously but consideration of its structure suggested that it is a tetraketide with proline (or equivalent) as the starter unit. This has now been confirmed by an incorpora­ tion experiment employing [l,2 -13C2]acetate as pre­ cursor and analysis of the isolated labelled product by 13C nuclear magnetic resonance spectroscopy (13C NMR). The basis for the experiment was the expectation that acetate would be incorporated into the resorcinol moiety by the usual acylphloroglucinol route (Scheme 1) while the acyl moiety, i.e ., the dichloropyrrole carboxylic acid residue, would be derived from the tricarboxylic acid (TCA) cycle as in Scheme 2. With the assumption that only the first two turns of the cycle would make a significant contribution, in­ tact acetate units would be incorporated into two bonds in this fragments, C -l, -2 and C-4, -5, which would be revealed by the presence of the characteris­ tic satellite patterns flanking the normal singlets for these four carbons in the 13C NMR spectrum. Since