Studies in the biosynthesis of virginiamycin S₁

Abstract

Some aspects of the biosynthesis of three amino acid residues in virginiamycin S₁ have been studied in Streptomyces virginiae by the incorporation of amino acid precursors labeled with either radioactive or stable isotopes. L-Lysine-U-¹⁴C was incorporated into both the 4-oxo-L-pipecolic acid and 3-hydroxypicolinic acid residues. The formation of the heterocyclic ring of both of these amino acids was shown to occur with retention of the nitrogen from the ε-amino group of lysine, as shown by the incorporation of DL-lysine-6-¹³C-6-¹⁵N. In addition, the 3-hydroxypicolinic acid residue incorporated deuterium from (2RS, 5R)-lysine-5-d₁, but not from (2RS, 5S)-lysine-5-d₁. This finding indicates that the 5-pro-(R) hydrogen of L-lysine is retained during the biogenesis of 3-hydroxypicolinic acid. In the conversion of L-phenylalanine to L-phenylglycine, the amino group moves to the benzylic position. This process could proceed either by an intermolecular mechanism, in which the original nitrogen is lost, or by an intramolecular mechanism, in which that nitrogen is retained. Administration of (RS)-phenylalanine-3-¹³C-¹⁵N resulted in its incorporation with loss of the labeled nitrogen. The process therefore occurs by an intermolecular mechanism.