Biosynthesis of L-671,329, an echinocandin-type antibiotic produced by Zalerion arboricola: origins of some of the unusual amino acids and the dimethylmyristic acid side chain

Abstract

The biosynthesis of L-671,329, an antibiotic of the echinocandin class, was studied in Zalerion arboricola by stable isotope tracer techniques and high-field NMR spectroscopy. The organism incorporates DL-(2-13C)tyrosine into the antibiotic with the label appearing as C-3 of the homotyrosine residue; the C-2 position of this residue can be labeled by (2- 13C)acetate. Thus, homotyrosine arises from tyrosine by a chain elongation mechanism involving condensation with acetate. (2-13C) Acetate also labels all the even-numbered carbon atoms (C-2-C-14) of the myristic acid side chain. L-(13CH3)Methionine does not donate its methyl group to 3-hydroxy-4-methylproline but is the origin of both methyl moieties of the 10,12-dimethylmyristoyl side chain. L-(l-13C)Proline is incorporated into only one of the two substituted proline residues, viz, 4-hydroxyproline. Label from L-(2-13C)leucine enriches the 3-hydroxy-4-methylproline residue, suggesting that this proline moiety is formed by cyclization of leucine.