2-Amino-2-deoxyisochorismate Is a Key Intermediate in Bacillus subtilis p-Aminobenzoic Acid Biosynthesis

Abstract

Chorismate is an important and central metabolite branching off to the biosyntheses of aromatic amino acids and p-aminobenzoic acid (pABA), a component of the vitamin folic acid. Here we report on a novel variation of a unified catalytic mechanism in Bacillus subtilis pABA biosynthesis that includes the formation of a new intermediate, 2-amino-2-deoxyisochorismate (ADIC), thus significantly differing from the mechanism in Escherichia coli. In B. subtilis, chorismate is converted to ADIC, which is catalyzed by aminodeoxychorismate synthase (ADCS). In a second step, ADIC is converted to aminodeoxychorismate (ADC) by addition of ammonia to C4, also catalyzed by ADCS. The third step is the aminodeoxychorismate lyase-catalyzed elimination of pyruvate from ADC. To our knowledge, B. subtilis aminodeoxychorismate synthase is the first enzyme exhibiting ADIC synthase activity in primary metabolism. We further provide evidence that pABA biosynthesis via ADIC might be a common mechanism for several other microorganisms.