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

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-C-13]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-C-13]acetate. Thus, homotyrosine arises from tyrosine by a chain elongation mechanism involving condensation with acetate. [2-C-13]Acetate also labels all the even-numbered carbon atoms (C-2-C-14) of the myristic acid side chain. L-[(CH3)-C-13]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-[1-C-13]Proline is incorporated into only one of the two substituted proline residues, viz, 4-hydroxyproline. Label from L-[2-C-13]leucine enriches the 3-hydroxy-4-methylproline residue, suggesting that this proline moiety is formed by cyclization of leucine.