Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes

Abstract

Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness.

Fig. 1

Representative phenazine structural derivatives. Phenazine methosulfate and neutral red are commonly used phenazine derivatives. Phenazine-1-carboxylic acid, 2-hydroxy-phenazine-1-carboxylic acid and 2-hydroxy-phenazine are produced by P. chlororaphis strain 30-84. Pyocyanin is produced by P. aeruginosa. MLN944 is a DNA-binding agent inhibitory to marine and human tumors (Sappal et al. 2004). Methanophenazine is produced by the Archaea Methanosarcina mazei Gö1. Descriptions are provided in the text

Fig. 2

Phenazine biosynthesis [Figure modified from Mentel et al. (2009)]. Phenazines are derived from the shikimic acid pathway that is highly conserved in most organisms. Chorismic acid serves as the phenazine branch point once the phenazine biosynthetic genes (phzABCDEFG) are expressed (note phzB, phzD, phzE, phzF and phzG are considered the five core genes). PhzC, the third enzyme in the phenazine operon, is a type II-3-deoxy-d-arabinoheptulosonate-7-phosphate that probably ensures sufficient substrate flow through the shikimic acid pathway for phenazine biosynthesis. The early steps of phenazine biosynthesis are becoming well elucidated while several of the later steps are not yet completely understood and differences may reflect variation in the final biosynthetic steps among microorganisms. From PCA a number of derivatives are formed by additional terminal modifying genes (not shown). For a thorough discussion of the pathway please see Mentel et al. (2009).Abbreviations: DAHP: 3-deoxy-d-arabinoheptulosonate 7-phosphate, Gln: glutamine, Glu: glutamic acid, ADIC: 2-amino-2-desoxyisochorismic acid, DHHA: trans-2,3-dihydro-3-hydroxyanthranilic acid, PCA: phenazine-1-carboxylic acid

Fig. 3

Representative effects of phenazines on cellular physiology, gene expression, host functions and biotechnological applications. In the center is the basic phenazine structure lacking any additional modifications. Details of the effects of phenazine derivatives on specific functions are described in the text