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.

Infection with Conditionally Virulent Streptococcus pneumoniae Δ pab Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

“…(23,38). Many bacteria and plants have the ability to synthesize PABA, but higher organisms do not (3,34), which makes the PABA biosynthetic pathway an attractive target for new vaccination and therapeutic strategies (18, 36). Genome-wide searches with S. pneu- (42).…”

“…Genome-wide searches with S. pneu- (42). In bacteria, PABA biosynthesis is generally believed to proceed via a two-step process requiring the presence of two enzymes, ADC synthase and ADC lyase (3,28,34,39,42). ADC lyase is encoded by the gene pabC and cleaves ADC to generate PABA and pyruvate (8).…”

Structure and Catalytic Mechanism of Yeast 4-Amino-4-deoxychorismate Lyase

“…1): first, ADC is synthesized from chorismate and glutamine; and second, ADC is converted to PABA (22). As an exception, the PABA biosynthesis pathway in Bacillus subtilis contains three steps; in the first step chorismate is converted to 2-amino-2-deoxyisochorismate (23).…”

Antituberculosis Agents and an Inhibitor of the para‐Aminobenzoic Acid Biosynthetic Pathway from Hydnocarpus anthelminthica Seeds

“…), and two known ones, namely chaulmoogric acid (4) and ethyl chaulmoograte (5). Their structures were determined mainly by using spectroscopic techniques.…”

“…Among biosynthetic pathways, chorismate is an important and central biosynthetic metabolite that branches off to the biosynthesis of p-aminobenzoic acid (pAba). The biosynthesis of pAba is known to take place in plants, fungi, prokaryotes, and parasites but not in humans; therefore, this pathway is expected to be an ideal target for the development of novel antibiotics [4] [5]. Medicinal plants have been used for years to combat infection diseases, and several antimicrobial agents have been successfully identified [6].…”