Stereochemical aspects of virginiamycin biosynthesis: biosynthesis of antibiotic A33853

Abstract

The biochemical pathways for the formation of the unusual amino acids found in virginiamycin M₁ and A33853 were investigated. Specifically tritiated and carbon 14 labeled serines were incorporated into virginiamycin M₁. (2S)-serine and (2S,3R)-[3-³H] serine were found to be precursors, thus giving evidence of stereochemical control in the formation of the oxazole moiety. This information allowed for postulation of a ring closure pathway. Stereochemical investigations were also carried out on the dehydroproline unit and it was shown that both (R) and (S) prolines were incorporated into the dehydroproline unit. (2S,3R)-[3-³H] proline was synthesized and upon incorporation lost the (3-³H) label as evidence of stereochemical control in the formation of the dehydroproline unit from a saturated precursor.

The basic biosynthetic origins of A33853 were investigated by feeding of D-[U-¹⁴C] glucose, sodium [U-¹⁴C] acetate, (S)-[U-¹⁴C] lysine, (S)-[U-¹⁴C] aspartic acid, [carboxyl-¹⁴C] anthranilic acid, and (S)-[5-³H] tryptophan. D-[U-¹⁴C]. Glucose and (S)-[U-¹⁴C] lysine appeared to be the main precursors. ¹³C¹⁵N lysine was synthesized and used to examine the ring closure of the 3-hydroxypicolinic amide ring in virginiamycin S₁.