Regulation of Phenazine Biosynthesis

Abstract

Microbiologists have historically been struck by both the beautiful pigmentation of phenazine-producing cultures and the high degree of variability in phenazine production among isolates, conditions, and even repeat experiments. Motivated by an interest in controlling phenazine biosynthesis, they have identified many of the factors that affect the regulation of this process. Phenazine production is controlled by complex regulatory networks. The variability of phenazine production can be explained in part by the effects of environmental conditions on these networks and by strain-specific differences in these networks. In this chapter, we describe the components of a common regulatory cascade that is represented in many phenazine-producing pseudomonads. Membrane sensor proteins and two component sensors control the activity of downstream regulators such as quorum sensing systems and RNA-binding proteins and small RNAs; these cytoplasmic regulators then control the production of phenazine biosynthetic proteins. We highlight examples from specific strains and cases where the mechanistic links may vary among them. We also discuss environmental parameters that have been shown to affect phenazine biosynthesis and compare their effects in different isolates. Ongoing work will further elaborate the details of the environmental sensing and regulatory responses that control production of these dramatically colored compounds. New findings have the potential to support enhanced application of phenazine-producing strains in agriculture, where they promote crop health, and the treatment of infections in which phenazines contribute to bacterial pathogenicity.

Characterization of the multiple molecular mechanisms underlying RsaL control of phenazine‐1‐carboxylic acid biosynthesis in the rhizosphere bacterium Pseudomonas aeruginosa PA1201

“…The genome of most P. aeruginosa strains also contains the phzM, phzS, and phzH genes, which encode terminalmodifying enzymes responsible for PCA conversion into the phenazine derivatives PCN and PYO (Chin-A-Woeng et al, 2001;Mavrodi et al, 2001). Phenazines biosynthesis in pseudomonads is governed by a complex regulatory network comprised of quorum sensing (QS) and two-component systems, small noncoding RNAs (sRNAs), and a number of specific and global transcriptional regulators (Wagner et al, 2003;Williams and C amara, 2009;Sonnleitner and Haas, 2011;Balasubramanian et al, 2013;Sakhtah et al, 2013). This regulatory network allows stringent modulation of phenazines biosynthesis in response to population dynamics and various environmental stimuli including temperature, pH, oxygen and nutrient availability (Duan and Surette, 2007;Huang et al, 2009;Recinos et al, 2012;Sakhtah et al, 2013;Cabeen, 2014).…”

Engineering mediator-based electroactivity in the obligate aerobic bacterium Pseudomonas putida KT2440

“…In the MET model organism P. aeruginosa , phenazine synthesis is tightly controlled by the cell-to-cell communication quorum sensing system, and also by environmental factors like oxygen or iron availability (Sakhtah et al, 2014 ). The synthesis is based on chorismate as a precursor and proceeds via the core phenazine molecule phenazine-1-carboxylic acid (PCA) to fan out to the derivatives pyocyanin (PYO), 1-hydroxyphenazine (1-OHPHZ), and phenazine carboxamide (PCN), each with different redox properties (Wang and Newman, 2008 ; Mentel et al, 2009 ).…”

Isolation and structure elucidation of phenazine derivative from Streptomyces sp. strain UICC B-92 isolated from Neesia altissima (Malvaceae)

“…Many phenazine-producing microorganisms belong to the bacterial phyla Actinobacteria and Proteobacteria, and the archaeal phylum Euryarcheota (37). The phenazine production among species, isolates, and even repeat cultivations of the same strain are often variable (38). It is probably due to subtle discrepancies in the regulatory networks and sensing mechanisms of the same strain (38).…”

“…The phenazine production among species, isolates, and even repeat cultivations of the same strain are often variable (38). It is probably due to subtle discrepancies in the regulatory networks and sensing mechanisms of the same strain (38). In natural systems, multiple derivatives or an individual phenazines play multiple roles in the bacterial interactions and behaviors (39), for example member of the genus Streptomyces (40).…”