Sj. Gould et al., 3-AMINO-4-HYDROXYBENZOIC ACID IS DERIVED FROM THE TRICARBOXYLIC-ACID CYCLE RATHER THAN THE SHIKIMIC ACID PATHWAY, Journal of the American Chemical Society, 118(39), 1996, pp. 9228-9232
The biosynthesis of 4-hydroxy-3-nitrosobenzamide in Streptomyces muray
amaensis mutants MC2 and MC3 has been studied using sodium [1,2-C-13(2
)]- and [1-C-13,O-18(2)]acetate, sodium [2,3-C-13(2)]succinate, [1,2-C
-13(2)]glutamic acid, [4-C-13]aspartic acid, and sodium [1-C-13]- and
[2,3-C-13(2)]pyruvate. C-13 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-carb
on unit, possibly phosphoenol pyruvate. Subsequent specific incorporat
ions of the labeled succinic acid, aspartic acid, and glutamic acid co
nfirmed the TCA cycle involvement and the orientation of the four-carb
on intermediate. Specific incorporation of the labeled pyruvic acids c
onfirmed the involvement of a three-carbon unit and defined its orient
ation. This is the first aminohydroxybenzoic acid derivative shown not
to be derived from a shikimic acid-type pathway, and its origin provi
des a rationale for the biosynthesis of other microbial products such
as asukamycin, manumycin, and the michigazones.