Phenazine-1,6-dicarboxylate and its dimethyl ester as precursors of other phenazines in bacteria

Abstract

We have previously described the use of biosynthetically formed ring-14C-labelled phenazines to investigate their further metabolism [1]. On the basis of results obtained with phenazine pigmentation mutants of a pseudomonad, a branched pathway has been proposed in which phenazine-1,6-dicarboxylate (PZ-1,6-diCOOH) is a key branchpoint compound [2]. Although it has been shown that PZ-1,6-diCOOH (I) acts as a precursor of other phenazines in Streptomyces species [3,4] its metabolism by pseudomonads could not be detected [1,2,4]. It is also known that PZ-1,6-diCOOH is inactive as a precursor of the phenazine iodinin in Brevibacterium iodinum [5]. These negative results may be due to a permeability barrier restricting the uptake of PZ-1,6-diCOOH in these organisms. This hypothesis is reinforced by the report that phenazine-l,6-dicarboxylate dimethyl ester (PZ-1,6-diCOOMe) (II), but not the free acid, acted as a precursor of phenazine-1-carboxylate in Pseudomonas aureofaciens [6]. The conversion of PZ-1,6-diCOOH to phenazine-1-carboxylate by P. aureofaciens whose permeability had been affected by ether treatment has also been shown [7]. These observations prompted us to prepare both