Biosynthesis of the polyoxins, nucleoside peptide antibiotics: a new metabolic role for L-isoleucine as a precursor for 3-ethylidene-L-azetidine-2-carboxylic acid (polyoximic acid).
The biosynthetic origin of the carbon skeleton of 3-ethylidene-L-azetidine-2-carboxylic acid (polyoximic acid) is described. This unique cyclic amino acid is the C terminus of the nucleoside peptide antibiotics, the polyoxins, elaborated by Streptomyces cacaoi var, asoensis. In vivo experiments show that 14-C from [1-14-C]isoleucine, [U-14-C]isoleucine, [1-14-C]methionine, [U-14-C]methionine, [U-14-C]threonine, and [1-14-C]glutamate is incorporated into polyoximic acid; however, 14-C from [5-14-C]glutamate and [methyl-14-C]methionine is not incorporated. The distribution of 14-C in polyoximic acid clearly shows that the intact carbon skeleton of L-isoleucine is utilized directly. The incorporation of 14-C from [U-14-C]methionine, [U-14-C]threonine, and [1-14-CA1glutamate into polyoximic acid occurred only after their conversion to isoleucine via 2-ketobutyrate. A scheme is presented in which either of the two beta-unsaturated amino acids isolated from Bankera fuligineoalba, L-2-amino-3-hydroxymethyl-3-pentenoic acid or L-2-amino-3-formyl-3-penetenoic acid, is regarded as a possible intermediate amino acid between isoleucine and polyoximic acid.
D000935:Antifungal Agents / Q000096:biosynthesis*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis*; D001385:Azetines / Q000096:biosynthesis*; D005971:Glutamates / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008956:Models, Chemical; D009705:Nucleosides / Q000096:biosynthesis; D010452:Peptide Biosynthesis; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
D000935:Antifungal Agents; D001385:Azetines; D005971:Glutamates; D009705:Nucleosides; D007532:Isoleucine; C010624:polyoximic acid; D013912:Threonine; D001383:Azetidinecarboxylic Acid; D008715:Methionine