Biosynthesis of Phenazine Antibiotics inStreptomyces antibioticus:  Stereochemistry of Methyl Transfer from Carbon-2 of Acetate

Abstract

Stable isotope labeling experiments have shown that the biosynthesis of the monomeric phenazines, the saphenyl esters, and their dimerization products, the esmeraldins, in Streptomyces antibioticus Tu ¨2706 proceeds from phenazine-1,6-dicarboxylic acid by chain extension with C-2 of acetate to 6-acetylphenazine-1-carboxylic acid, which is reduced to saphenic acid. The latter is incorporated into both halves of the esmeraldins, albeit differentially. By feeding of chiral acetate, degradation of the resulting saphenyl esters and esmeraldins, and configurational analysis of the acetic acid formed, the chain extension process was found to proceed with overall inversion of configuration at the methyl group. This suggests that the decarboxylation of a hypothetical intermediate β-keto acid proceeds in an inversion mode. This result is discussed with reference to analogous C-methylations of polyketide backbones by addition of C-2 of acetate.

Bioactive Secondary Metabolites with Unique Aromatic and Heterocyclic Structures Obtained from Terrestrial Actinomycetes Species

“…30) The known phenazine-1-carboxylic acid (22), 26) phencomycin (23), 31) and phenazine-1,6-dicarboxylic acid (24) 24) were also isolated (Fig. 5).…”

“…The phenazine derivatives izumiphenazines A-D (12-15) 22,23) along with the known phenazine-1,6-dicarboxylic acid, 24) 1-hydroxyphenazine, 25) phenazine-1-carboxylic acid, 26) and 6-hydroxyphenazine-1-carboxylic acid 27) were isolated from the ethyl acetate extract of Streptomyces sp. IFM 11204 (Fig.…”

Isolation of phenazine 1,6-di-carboxylic acid from Pseudomonas aeruginosa strain HRW.1-S3 and its role in biofilm-mediated crude oil degradation and cytotoxicity against bacterial and cancer cells

“…However, the hypothesis was rejected by McDonald and coworker (McDonald et al 1999) where it has been shown that PDC cannot be an intermediate in the formation of PCA as the decarboxylation is integral in dimerization process. However, studies on Streptomyces by various groups depict the role of PDC in the formation of lumofungin, iodinin, sephenamycin, and esmeraldins (McDonald et al 1999;Buckland et al 1981;Messenger and Turner 1983). In recent past, Rui and coworkers established the role of genes EsmA1 and EsmA2 in the yield of PDC during biosynthesis of esmeraldins from Steptomyces antibioticus Tü 2706 (Rui et al 2012).…”

New pyranonaphthoquinones and a phenazine alkaloid isolated from Streptomyces sp. IFM 11307 with TRAIL resistance-overcoming activity

“…The molecular weight of compound 2 was determined to be 418 Da from the positive ion mode of (+)-ESI mass spectroscopy. The molecular formula was determined to be C 21 The spectral data (including NMR and MS) of compounds 3 and 4 were identical with those of 4¢-deacetyl-griseusin A and B, respectively, which indicated the same relative stereochemistry. A further interesting observation was that compounds 3 and 4 also possess opposite signs of optical rotation values and CD spectra to those of (À)-4¢-deacetyl-griseusin A and B.…”

“…18 The known compound 6 was easily identified as phenazine-1,6-dicarboxylic acid based on the NMR data and by comparison with the reference values. 21 …”