Study to the biosynthesis of the rifamycin-chromophore in Nocardia mediterranei.

Nocardia mediterranei produces the antibiotic rifamycin B, which belongs to the ansamycin group. The structure of rifamycin consists of the ansa chain and the chromophore. One part of this chromophore, the seven-carbon amino unit, which initiates ansa chain formation in ansamycins, has been identified as 3-amino-5-hydroxybenzoic acid. Kibby et al. 1] synthesized [carboxy-14C]3-amino-5hydroxybenzoic acid and showed that this labeled compound was incorporated into the ansamycin actamycin. Ghisalba and Nuesch2}, using a different approach, came to the same result with rifamycin from N. mediterranei. By supplementing mutant A8 (transketolase", synthesizes only 10% of the rifamycin B produced by the parent)3) with 3-amino-5-hydroxybenzoic acid, they found a strong stimulation of the rifamycin B production, which was comparable to the titer reached with the parent strain N813. The seven-carbon amino unit itself is derived from an intermediate in the mainsequence of the aromatic amino acid biosynthesis. By chemical and biochemical analysis of mutant A8 and mutant A104) (shikimate accumulation, aro~\ rifamycin+) if was demonstrated that the branch point is located between 3-deoxy-D-arabinoheptulosonic acid 7phosphate (DAHP) and shikimic acid. Four pathways for the biosynthesis of 3-amino-5hydroxybenzoic acid would therefore be possible (Fig. 1). Hornemann et al.5) proposed acyclic