THE BIOSYNTHESIS OF SULFOMYCIN ELUCIDATED BY ISOTOPIC LABELING STUDIES

U-102408 has been isolated from S. arginensis cultures and fully chara cterized by NMR and MS, These studies indicate that U-102408 is identi cal with sulfomycin, and this data confirm the structure of sulfomycin which was assigned by chemical degradation and limited NMR studies. T he biosynthetic origins of all U-102408 structural features have been elucidated through isotopic labeling experiments with primarily C-13 b ut also using C-14, deuterium or tritium. Of particular interest, the 4-hydroxy-2-amino-2-pentenoic acid moiety was determined to originate from threonine and a one carbon unit derived from the two position of glycine or the S-methyl of methionine. The biosynthetic pathway for U- 102408 differs from that for nosiheptide, thiostrepton, and berninamyc in in that cysteine and serine do not cross label sites in U-102408, w hile this has been observed for the other thiopeptides, In U-102408 cy steine and serine are each incorporated into unique sites within the m olecule. This indicates that the interconversion of cysteine and serin e is not an active pathway for S. arginensis. In fact for fermentation s in defined medium the addition of cysteine was found to be necessary to achieve higher antibiotic titer, Unlike the other thiopeptides tha t have been studied, threonine was incorporated into sites labeled by serine though serine did not incorporate into sites labeled by threoni ne within U-102408, No cross labeling of threonine and serine has been observed in studies of nosiheptide, thiostrepton, or berninamycin. In the current study glycine is investigated as a precursor for U-102408 . The interconversion of glycine to serine is a very facile pathway in S. arginensis; glycine labels all sites labeled by serine. This data suggests glycine as a possible precursor for nosiheptide, thiostrepton , and berninamycin which has not been investigated for these other thi opeptides. Incorporation of label from 3-H-2-serine is facile for thio strepton and nosiheptide and was used to probe the mechanism of format ion of the pyridine ring, However, no incorporation from 3-H-2-serine or 3-H-3-serine was observable for U-102408. While the lack of incorpo ration may be due to washout of the label from the precursor, it also may be due to the interconversion of serine and glycine causing loss o f the label from the serine pool.