Biosynthesis of the aurovertins B and D. The role of methionine and propionate in the simultaneous operation of two independent biosynthetic pathways

Abstract

The complete assignment of the natural abundance ¹³C n.m.r. spectra of the aurovertins B (1) and D (2), toxic metabolites isolated from Calcarisporium arbuscula NRRL 3705, permitted a study of their biosynthetic origin using the following ¹³C-labelled precursors: [1-¹³C]-, [2-¹³C]-, [1,2-¹³C]-, and [2-¹³C, 2-²H₃]-acetate, (2S)-[methyl-¹³C]methionine, [2-¹³C]malonate, and [1-¹³C]- and [3-¹³C]propionate. The results show that both the aurovertins B and D can be formed via two biosynthetic pathways which are distinguishable by the different origins of C(1)–C(3). The first pathway involves the C-methylation of a C₂₀-polyketide precursor at C₁₈, followed by the loss of the chain-initiating acetate unit, C₁₉–C₂₀; C(1) in the aurovertins is thus derived from methionine and C(2) and C(3) from malonate. The second pathway involves a C₁₉-precursor, formed from a propionate chain-initiating unit and eight malonate units; C(1)–C(3) are derived from propionate. The simultaneous operation of two independent pathways in the biosynthesis of the aurovertins B and D is unique amongst fungal metabolites.