Pseudomonic acid biosynthesis. The putative role of 3-hydroxy-3-methylglutarate

Abstract

The putative role of 3-hydroxy-3-methylglutarate (HMG) as a precursor in pseudomonate biosynthesis has been investigated by the efficient ozonolysis of the Δ C2–C3 of methyl pseudomonate A to give a C₁₆ ketone moiety, allowing comparison of the incorporation of small additions of [1-¹⁴C]acetate, [3-¹⁴C] HMG and [1,5-¹⁴C]HMG to fermentations during pseudomonate biosynthesis. Half of the radioactivity of the pseudomonate from all precursors was in the C₁₆ moiety, which would not be radiolabelled by [1,5-¹⁴C]HMG if HMG is a direct precursor. Prior degradation of HMG to acetate, the interpretation of a previous ¹³C experiment, is implied and further supported by the extent of incorporation of [3-¹⁴C]HMG heavily diluted with unlabelled HMG. Although new hypotheses may be required to define pseudomonate biosynthesis, Pseudomonas fluorescens may degrade all exogenous HMG, however sparingly administered, and foil its use as an effective biosynthetic probe.