Phenazine-1,6-dicarboxylic acid — an intermediate in phenazine biosynthesis?

Tetrahedron Letters
1978.0

Abstract

Consideration of structural relationships between the various microbial phenazines, in association with evidence on the manner of shikimic acid incorporation, leads to phenazine-1,8-dicarboxylic acid (I) as a likely common intermediate. Labelled (I) has been found, however, not to be incorporated into pyocyanin (3) in Pseudomonas aeruginosa, phenazine-I-carboxylic acid (4) in P. aureofaciens, or iodinin (6) in Brevibacterium iodinum, and we have been unable to trap (I) during a feeding experiment with P. aureofaciens. Dimethyl phenazine-1,8-dicarboxylate (2), labelled with 14C in the carboxy-groups, showed a total incorporation in excess of 0.2% into (4) and (5) in P. aureofaciens. The dihydro-derivative (7) of (I) was also not incorporated to a significant extent (0.2%) into (4) and (5) in P. aureofaciens. However, (I) showed high incorporations (6.7 and 9.0%) into lomofungin (8) in Streptomyces lomodensis (assayed on the penta-acetate by recrystallization to constant activity), indicating phenazine-1,8-dicarboxylic acid (I) is clearly a lomofungin (8) precursor. We are currently investigating whether (I) is a precursor only for phenazines with two aryl-C1 substituents [as (8)] or whether it is transported across the cell walls of Streptomyces species but not those of Pseudomonas and Brevibacterium species.

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