Phenazines

Phenazine is an organic compound with the formula (C6H4)2N2. It is a dibenzo annulated pyrazine, and

the parent substance of many dyestuffs, such as the toluylene red, indulines, and safranines (and

the closely related eurhodines). Phenazine crystallizes in yellow needles, which are only sparingly

soluble in alcohol. Sulfuric acid dissolves it, forming a deep-red solution.

Phenazines are heterocyclic, nitrogenous compounds differ in their chemical and

physical properties. Bacteria are the known resource of natural phenazines. Phenazines

are important for their potential impact on bacterial interactions and biotechnological

processes. It also exhibits a wide range of biological activities. Streptomyces sp.

SpC080624SC-11 associated with the marine sponge Cinachyra sp. produced

novel isoprenoids such as JBIR-46, -47, and -48. The structures of JBIR-46 , -47 , and

-48 were identified as phenazine derivatives harboring dimethylallyl moieties .

Furthermore, Streptomyces sp. Sp080513GE-23 produced fumaquinone

through mevalonate pathway. All these compounds showed cytotoxic activity against

human acute myelogenous leukemia HL-60 cells . Schneemann et al.  designed the

primers for phzE gene involved in the phenazine biosynthetic pathway to investigate the

diversity of phenazine-producing bacteria including actinobacteria from the Halichondria

panicea and Saccharina latissima. The results demonstrated that the actinobacteria

could produce different types of phenazine such as endophenazines, phenazine-1,6-

dicarboxylic acid, and chlororaphin. Interestingly, we screened the phenazines

production in the sponges of Yongxing and Xisha Islands of the South China Sea.

Based on the gene screening and level of phzE gene expression 1,6-dihydroxy

phenazine from Nocardiopsis sp. 13-33-15 and 13-12-13, and 1,6-dimethoxy phenazine

from Nocardiopsis sp. 13-33-15 were isolated and identified successfully based on ESI-
MS and NMR analysis. Both compounds showed antibacterial activity against Bacillus

mycoides SJ14, Staphylococcus aureus SJ51, Escherichia coli SJ42, and Micrococcus

luteus . Streptomyces sp. isolated from the sponge Halichondria panicea of Baltic Sea,

Germany, produced streptophenazines A–H . Subinhibitory concentrations of antibiotics

in the culture media modulated the pattern of streptophenazine production.

Streptophenazines C and H showed modest activity against Bacillus subtilis.

Additionally, streptophenazine C also showed a modest activity against Staphylococcus

lentus . Two new phenazines, 6-hydroxymethyl-1-phenazine-carboxamide and 1, 6-

phenazinedimethanol , were isolated from the culture broth of Brevibacterium sp. KMD

003-associated Callyspongia sp. (Kyeongpo, Gangwondo, Korea). These two

phenazines showed antibacterial activities against Enterococcus hirae and Micrococcus

luteus with 5 μM MIC values [94]. Cocultivation of Actinokineospora sp. EG49

and Nocardiopsis sp. RV163 produced 1,6-dihydroxyphenazine . It was active

against Bacillus sp. P25, Trypanosoma brucei and interestingly,

against Actinokineospora sp. EG49 [74]. The chemical structures of phenazines are

shown in Fig. .