3-Amino-4-hydroxybenzoic Acid Is Derived from the Tricarboxylic Acid Cycle Rather Than the Shikimic Acid Pathway1

• Published in: Journal of the American Chemical Society Vol. 118; no. 39; pp. 9228 - 9232
• Main Authors: Gould, Steven J, Melville, Chris R, Cone, Martha C
• Format: Journal Article
• Language: English
• Published: American Chemical Society 02.10.1996
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9524356

The biosynthesis of 4-hydroxy-3-nitrosobenzamide in Streptomyces murayamaensis mutants MC2 and MC3 has been studied using sodium [1,2-13C2]- and [1-13C,18O2]acetate, sodium [2,3-13C2]succinate, [1,2-13C2]glutamic acid, [4-13C]aspartic acid, and sodium [1-13C]- and [2,3-13C2]pyruvate. 13C NMR analysis of the labeling patterns from the first two of these suggested a pathway via condensation of a four-carbon unit from the tricarboxylic acid (TCA) cycle with a three-carbon unit, possibly phosphoenol pyruvate. Subsequent specific incorporations of the labeled succinic acid, aspartic acid, and glutamic acid confirmed the TCA cycle involvement and the orientation of the four-carbon intermediate. Specific incorporation of the labeled pyruvic acids confirmed the involvement of a three-carbon unit and defined its orientation. This is the first aminohydroxybenzoic acid derivative shown not to be derived from a shikimic acid-type pathway, and its origin provides a rationale for the biosynthesis of other microbial products such as asukamycin, manumycin, and the michigazones.