Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthetic conversion of tyrosine to the C2- and C3-proline moieties of anthramycin, tomaymycin, and sibiromycin.
This paper descirbes biosynthetic labeling experiments on the conversion of tyrosine to the C2- and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The biosynthetic fate of all of the aromatic and side-chain hydrogens has been determined in each antibiotic by using dual tagged (3H/14C) and 2H-labeled tyrosine molecules. In addition, experiments uing [15N]tyrosine and the tritiated D and L isomers of tyrosine have shed some light on the biochemical reactions which take place at tha alpha position of tyrosine. On the basis of results of all these experiments, a biosynthetic scheme had been proposed to rationalize the apparent inconsistencies which occur between the results for the three antibiotics. This scheme proposes that a common main pathway involving proximal extradiol cleavage of Dopa and condensation to form the pyrrolo ring leads ultimately to a C-7 branch point compound. Parallel pathways from this central branch point compound lead by well-known biochemical transformations to the C2-and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The reactions in these parallel pathways are suggested to be "cosmetic or after events".
D000192:Actinomycetales / Q000378:metabolism; D000876:Anthramycin / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D001570:Benzodiazepinones / Q000096:biosynthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011392:Proline / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001570:Benzodiazepinones; D000876:Anthramycin; D014443:Tyrosine; D011392:Proline