Recent Developments in the Biological Activities, Bioproduction, and Applications of Pseudomonas spp. Phenazines

Phenazines are a large group of heterocyclic nitrogen-containing compounds with demonstrated insecticidal, antimicrobial, antiparasitic, and anticancer activities. These natural compounds are synthesized by several microorganisms originating from diverse habitats, including marine and terrestrial sources. The most well-studied producers belong to the Pseudomonas genus, which has been extensively investigated over the years for its ability to synthesize phenazines. This review is focused on the research performed on pseudomonads’ phenazines in recent years. Their biosynthetic pathways, mechanism of regulation, production processes, bioactivities, and applications are revised in this manuscript.

[1]  Derrick Butler,et al.  Electrochemical Sensors Based on MoSx‐Functionalized Laser‐Induced Graphene for Real‐Time Monitoring of Phenazines Produced by Pseudomonas aeruginosa , 2022, Advanced healthcare materials.

[2]  B. Kim,et al.  Enhanced co-production of medium-chain-length polyhydroxyalkanoates and phenazines from crude glycerol by high cell density cultivation of Pseudomonas chlororaphis in membrane bioreactor. , 2022, International journal of biological macromolecules.

[3]  Hong-bo Hu,et al.  Enhanced Phenazine-1-Carboxamide Production in Pseudomonas chlororaphis H5△fleQ△relA through Fermentation Optimization , 2022, Fermentation.

[4]  Xiaonan Xie,et al.  Regulation of phenazine-1-carboxamide production by quorum sensing in type strains of Pseudomonas chlororaphis subsp. chlororaphis and Pseudomonas chlororaphis subsp. piscium. , 2022, Journal of bioscience and bioengineering.

[5]  Mo Xian,et al.  Biosynthetic Pathway Construction and Production Enhancement of 1-Hydroxyphenazine Derivatives in Pseudomonas chlororaphis H18. , 2022, Journal of agricultural and food chemistry.

[6]  Wei Wang,et al.  Uncovering the Role of PhzC as DAHP Synthase in Shikimate Pathway of Pseudomonas chlororaphis HT66 , 2022, Biology.

[7]  R. Isticato,et al.  Pseudomonas fluorescens Showing Antifungal Activity against Macrophomina phaseolina, a Severe Pathogenic Fungus of Soybean, Produces Phenazine as the Main Active Metabolite , 2021, Biomolecules.

[8]  Weiwei Liu,et al.  Advances in Phenazines over the Past Decade: Review of Their Pharmacological Activities, Mechanisms of Action, Biosynthetic Pathways and Synthetic Strategies , 2021, Marine drugs.

[9]  Cheryl Stephen Jeganathan,et al.  Extraction, purification and characterization of phenazine from Pseudomonas aeruginosa isolate of wastewater sources: a panacea towards clinical pathogens , 2021, Applied Nanoscience.

[10]  A. Raio,et al.  Pseudomonas chlororaphis metabolites as biocontrol promoters of plant health and improved crop yield , 2021, World Journal of Microbiology and Biotechnology.

[11]  D. Ramos,et al.  Benzo[a]phenazine derivatives: Promising scaffolds to combat resistant Mycobacterium tuberculosis , 2021, Chemical biology & drug design.

[12]  P. Laborda,et al.  Biocontrol ability of phenazine-producing strains for the management of fungal plant pathogens: A review , 2021 .

[13]  U. Vasconcelos,et al.  Colour Me Blue: The History and the Biotechnological Potential of Pyocyanin , 2021, Molecules.

[14]  M. Rosenbaum,et al.  Controlling the Production of Pseudomonas Phenazines by Modulating the Genetic Repertoire. , 2020, ACS chemical biology.

[15]  Mahaveer P. Sharma,et al.  Characterization of antifungal metabolite phenazine from rice rhizosphere fluorescent pseudomonads (FPs) and their effect on sheath blight of rice , 2020, Saudi journal of biological sciences.

[16]  Jiangyang Ou,et al.  Degradation, adsorption and leaching of phenazine-1-carboxamide in agricultural soils. , 2020, Ecotoxicology and environmental safety.

[17]  Xue‐Wen Liu,et al.  Anticancer activity, topoisomerase I inhibition, DNA ‘light switch’ behavior and molecular docking of two ruthenium complexes containing phenazine ring , 2020, Journal of biomolecular structure & dynamics.

[18]  F. Ye,et al.  Isolation and identification of bioactive substance 1-hydroxyphenazine from Pseudomonas aeruginosa and its antimicrobial activity. , 2020, Letters in applied microbiology.

[19]  Hong-bo Hu,et al.  Engineering of glycerol utilization in Pseudomonas chlororaphis GP72 for enhancing phenazine-1-carboxylic acid production , 2020, World Journal of Microbiology and Biotechnology.

[20]  Dawei Zhang,et al.  Pyocyanin-modifying genes phzM and phzS regulated the extracellular electron transfer in microbiologically-influenced corrosion of X80 carbon steel by Pseudomonas aeruginosa , 2020 .

[21]  Hong-bo Hu,et al.  Microbial Synthesis of Antibacterial Phenazine-1,6-dicarboxylic acid and the Role of PhzG in Pseudomonas chlororaphis GP72AN. , 2020, Journal of agricultural and food chemistry.

[22]  Hong-bo Hu,et al.  Enhanced production of 2-hydroxyphenazine from glycerol by a two-stage fermentation strategy in Pseudomonas chlororaphis GP72AN. , 2019, Journal of agricultural and food chemistry.

[23]  Hongfen Yang,et al.  Phenazine Antibiotic‐Inspired Discovery of Bacterial Biofilm‐Eradicating Agents , 2019, Chembiochem : a European journal of chemical biology.

[24]  A. Imran,et al.  Functional characterization of potential PGPR exhibiting broad-spectrum antifungal activity. , 2019, Microbiological research.

[25]  D. Joshi,et al.  An Overview on Common Organic Solvents and Their Toxicity , 2019, Journal of Pharmaceutical Research International.

[26]  T. Hsiang,et al.  The influence of steric configuration of phenazine-1-carboxylic acid-amino acid conjugates on fungicidal activity and systemicity. , 2019, Pest management science.

[27]  G. Andrade,et al.  Enhanced production of target bioactive metabolites produced by Pseudomonas Aeruginosa LV strain , 2019, Biocatalysis and Agricultural Biotechnology.

[28]  Hong-bo Hu,et al.  Enhanced biosynthesis of arbutin by engineering shikimate pathway in Pseudomonas chlororaphis P3 , 2018, Microbial Cell Factories.

[29]  Hong-bo Hu,et al.  Adsorption/desorption characteristics, separation and purification of phenazine‐1‐carboxylic acid from fermentation extract by macroporous adsorbing resins , 2018 .

[30]  Pingyuan Zhang,et al.  Enhanced biosynthesis of phenazine-1-carboxamide by engineered Pseudomonas chlororaphis HT66 , 2018, Microbial Cell Factories.

[31]  Andreas Norrman,et al.  Coherence lattices in surface plasmon polariton fields. , 2018, Optics letters.

[32]  Hong-bo Hu,et al.  Engineering and systems-level analysis of Pseudomonas chlororaphis for production of phenazine-1-carboxamide using glycerol as the cost-effective carbon source , 2018, Biotechnology for Biofuels.

[33]  L. Pierson,et al.  Effect of Producing Different Phenazines on Bacterial Fitness and Biological Control in Pseudomonas chlororaphis 30-84 , 2018, The plant pathology journal.

[34]  Hong-bo Hu,et al.  Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66 , 2018, Microbial Cell Factories.

[35]  Nikolaus Guttenberger,et al.  Recent developments in the isolation, biological function, biosynthesis, and synthesis of phenazine natural products. , 2017, Bioorganic & medicinal chemistry.

[36]  Hafiz M.N. Iqbal,et al.  Engineering Pseudomonas for phenazine biosynthesis, regulation, and biotechnological applications: a review , 2017, World journal of microbiology & biotechnology.

[37]  Hong-bo Hu,et al.  PhzA, the shunt switch of phenazine-1,6-dicarboxylic acid biosynthesis in Pseudomonas chlororaphis HT66 , 2017, Applied Microbiology and Biotechnology.

[38]  V. Kochetkov,et al.  Bioactive pigment production by Pseudomonas spp. MCC 3145: Statistical media optimization, biochemical characterization, fungicidal and DNA intercalation-based cytostatic activity , 2017 .

[39]  G. Andrade,et al.  The Effect of Phenazine-1-Carboxylic Acid on Mycelial Growth of Botrytis cinerea Produced by Pseudomonas aeruginosa LV Strain , 2017, Front. Microbiol..

[40]  Zhihong Xu,et al.  Synthesis and bioactivities of Phenazine-1-carboxylic acid derivatives based on the modification of PCA carboxyl group. , 2017, Bioorganic & medicinal chemistry letters.

[41]  Xiaonan Xie,et al.  Complete Genome Sequence of Pseudomonas chlororaphis subsp. aurantiaca Reveals a Triplicate Quorum-Sensing Mechanism for Regulation of Phenazine Production , 2017, Microbes and environments.

[42]  Rongxiu Li,et al.  A kinetic model for phenazine-1-carboxylic acid production by pseudomonas sp . M 18 G , 2017 .

[43]  S. Mehnaz,et al.  The Systematic Investigation of the Quorum Sensing System of the Biocontrol Strain Pseudomonas chlororaphis subsp. aurantiaca PB-St2 Unveils aurI to Be a Biosynthetic Origin for 3-Oxo-Homoserine Lactones , 2016, PloS one.

[44]  Hong-bo Hu,et al.  Genetic engineering of Pseudomonas chlororaphis GP72 for the enhanced production of 2-Hydroxyphenazine , 2016, Microbial Cell Factories.

[45]  Huasong Peng,et al.  iTRAQ-based quantitative proteomic analysis reveals potential factors associated with the enhancement of phenazine-1-carboxamide production in Pseudomonas chlororaphis P3 , 2016, Scientific Reports.

[46]  M. Laxmi,et al.  Characterization of pyocyanin with radical scavenging and antibiofilm properties isolated from Pseudomonas aeruginosa strain BTRY1 , 2016, 3 Biotech.

[47]  Xuehong Zhang,et al.  Engineering the central biosynthetic and secondary metabolic pathways of Pseudomonas aeruginosa strain PA1201 to improve phenazine-1-carboxylic acid production. , 2015, Metabolic engineering.

[48]  T. Sengupta,et al.  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 , 2015, Applied Microbiology and Biotechnology.

[49]  N. Sakthivel,et al.  5-Methyl phenazine-1-carboxylic acid: a novel bioactive metabolite by a rhizosphere soil bacterium that exhibits potent antimicrobial and anticancer activities. , 2015, Chemico-biological interactions.

[50]  B. Kumar,et al.  Characterization of the Bioactive Metabolites from a Plant Growth-Promoting Rhizobacteria and Their Exploitation as Antimicrobial and Plant Growth-Promoting Agents , 2015, Applied Biochemistry and Biotechnology.

[51]  Xuemei Shen,et al.  Comparative genomic analysis and phenazine production of Pseudomonas chlororaphis, a plant growth-promoting rhizobacterium , 2015, Genomics data.

[52]  W. Blankenfeldt,et al.  The structural biology of phenazine biosynthesis. , 2014, Current opinion in structural biology.

[53]  B. Kumar,et al.  Purification and characterization of antifungal phenazines from a fluorescent Pseudomonas strain FPO4 against medically important fungi. , 2014, Journal de mycologie medicale.

[54]  Hong-bo Hu,et al.  Reaction Kinetics for the Biocatalytic Conversion of Phenazine-1-Carboxylic Acid to 2-Hydroxyphenazine , 2014, PloS one.

[55]  E. Radhakrishnan,et al.  Phenazine carboxylic acid production and rhizome protective effect of endophytic Pseudomonas aeruginosa isolated from Zingiber officinale , 2014, World journal of microbiology & biotechnology.

[56]  D. Newman,et al.  Measurement of phenazines in bacterial cultures. , 2014, Methods in molecular biology.

[57]  Jian-xin Wang,et al.  Integrated biological and chemical control of rice sheath blight by Bacillus subtilis NJ-18 and jinggangmycin. , 2014, Pest management science.

[58]  W. Blankenfeldt,et al.  Trapped intermediates in crystals of the FMN-dependent oxidase PhzG provide insight into the final steps of phenazine biosynthesis. , 2013, Acta crystallographica. Section D, Biological crystallography.

[59]  S. Chincholkar,et al.  Microbial Phenazines , 2013, Springer Berlin Heidelberg.

[60]  A. Mostafa,et al.  Production and Optimization of Pseudomonas fluorescens Biomass and Metabolites for Biocontrol of Strawberry Grey Mould , 2012 .

[61]  L. Pierson,et al.  Differential regulation of phenazine biosynthesis by RpeA and RpeB in Pseudomonas chlororaphis 30-84. , 2012, Microbiology.

[62]  S. Shim,et al.  Elucidation of antifungal metabolites produced by Pseudomonas aurantiaca IB5-10 with broad-spectrum antifungal activity. , 2012, Journal of microbiology and biotechnology.

[63]  S. Hamza,et al.  Isolation and characterization of phenazine produced from mutant Pseudomonas aeruginosa , 2012 .

[64]  L. Vanhaecke,et al.  N-Acylhomoserine lactone quorum-sensing signalling in antagonistic phenazine-producing Pseudomonas isolates from the red cocoyam rhizosphere. , 2011, Microbiology.

[65]  Nicholas J. Jacobs,et al.  Antifungal mechanisms by which a novel Pseudomonas aeruginosa phenazine toxin kills Candida albicans in biofilms , 2010, Molecular microbiology.

[66]  Liu-yin Fan,et al.  Purification of low‐concentration phenazine‐1‐carboxylic acid from fermentation broth of Pseudomonas sp. M18 via free flow electrophoresis with gratis gravity , 2010, Electrophoresis.

[67]  Xuehong Zhang,et al.  Enhancement of phenazine-1-carboxylic acid production using batch and fed-batch culture of gacA inactivated Pseudomonas sp. M18G. , 2010, Bioresource technology.

[68]  R. Bourret,et al.  Two-component signal transduction. , 2010, Current opinion in microbiology.

[69]  L. Pierson,et al.  Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes , 2010, Applied Microbiology and Biotechnology.

[70]  Haixia Jiang,et al.  Optimization of phenazine-1-carboxylic acid production by a gacA/qscR-inactivated Pseudomonas sp. M18GQ harboring pME6032Phz using response surface methodology , 2010, Applied Microbiology and Biotechnology.

[71]  N. Mathivanan,et al.  Purification, crystal structure and antimicrobial activity of phenazine‐1‐carboxamide produced by a growth‐promoting biocontrol bacterium, Pseudomonas aeruginosa MML2212 , 2010, Journal of applied microbiology.

[72]  Hong-bo Hu,et al.  Enhanced production of 2-hydroxyphenazine in Pseudomonas chlororaphis GP72 , 2010, Applied Microbiology and Biotechnology.

[73]  F. Jamil,et al.  Characterization of a phenazine and hexanoyl homoserine lactone producing Pseudomonas aurantiaca strain PB-St2, isolated from sugarcane stem. , 2009, Journal of microbiology and biotechnology.

[74]  W. Blankenfeldt,et al.  Diversity and Evolution of the Phenazine Biosynthesis Pathway , 2009, Applied and Environmental Microbiology.

[75]  C. Ruangviriyachai,et al.  Isolation and Analysis of Antibacterial Substance Produced from P. aeruginosa TISTR 781 , 2009 .

[76]  R. Breinbauer,et al.  PhzA/B catalyzes the formation of the tricycle in phenazine biosynthesis. , 2008, Journal of the American Chemical Society.

[77]  Xuehong Zhang,et al.  Rapid quantitative analysis of phenazine-1-carboxylic acid and 2-hydroxyphenazine from fermentation culture of Pseudomonas chlororaphis GP72 by capillary zone electrophoresis. , 2008, Talanta.

[78]  Xuehong Zhang,et al.  Medium factor optimization and fermentation kinetics for phenazine‐1‐carboxylic acid production by Pseudomonas sp. M18G , 2008, Biotechnology and bioengineering.

[79]  Xuehong Zhang,et al.  Optimization of critical medium components using response surface methodology for phenazine-1-carboxylic acid production by Pseudomonas sp. M-18Q. , 2008, Journal of bioscience and bioengineering.

[80]  Xuehong Zhang,et al.  Optimization of nutrient components for enhanced phenazine-1-carboxylic acid production by gacA-inactivated Pseudomonas sp. M18G using response surface method , 2008, Applied Microbiology and Biotechnology.

[81]  Hong-bo Hu,et al.  Metabolic degradation of phenazine-1-carboxylic acid by the strain Sphingomonas sp. DP58: the identification of two metabolites , 2008, Biodegradation.

[82]  S. Chincholkar,et al.  Detection, isolation and identification of phenazine-1-carboxylic acid produced by biocontrol strains of Pseudomonas aeruginosa , 2007 .

[83]  S. R. Giddens,et al.  Investigations into the in vitro antimicrobial activity and mode of action of the phenazine antibiotic D-alanylgriseoluteic acid. , 2007, International journal of antimicrobial agents.

[84]  Xuehong Zhang,et al.  Characterization of a Phenazine-Producing Strain Pseudomonas chlororaphis GP72 with Broad-Spectrum Antifungal Activity from Green Pepper Rhizosphere , 2007, Current Microbiology.

[85]  W. Blankenfeldt,et al.  Phenazine compounds in fluorescent Pseudomonas spp. biosynthesis and regulation. , 2006, Annual review of phytopathology.

[86]  P. Slininger,et al.  Liquid-culture pH, temperature, and carbon (not nitrogen) source regulate phenazine productivity of the take-all biocontrol agentPseudomonas fluorescens 2-79 , 1995, Applied Microbiology and Biotechnology.

[87]  B. Lugtenberg,et al.  Regulatory roles of psrA and rpoS in phenazine-1-carboxamide synthesis by Pseudomonas chlororaphis PCL1391. , 2006, Microbiology.

[88]  D. Haas,et al.  Biological control of soil-borne pathogens by fluorescent pseudomonads , 2005, Nature Reviews Microbiology.

[89]  F. Wrede Über das Pyocyanin, den blauen Farbstoff des Bacillus pyocyaneus , 1930, Zeitschrift für Hygiene und Infektionskrankheiten.

[90]  L. Tong,et al.  Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[91]  E. Eisenstein,et al.  Structure and function of the phenazine biosynthesis protein PhzF from Pseudomonas fluorescens 2-79. , 2004, Biochemistry.

[92]  Xuehong Zhang,et al.  Phenazine-1-carboxylic acid is negatively regulated and pyoluteorin positively regulated by gacA in Pseudomonas sp. M18. , 2004, FEMS microbiology letters.

[93]  T. Chin-A-Woeng,et al.  Influence of environmental conditions on the production of phenazine-1-carboxamide by Pseudomonas chlororaphis PCL1391. , 2004, Molecular plant-microbe interactions : MPMI.

[94]  J. Nielsen,et al.  Phenazine natural products: biosynthesis, synthetic analogues, and biological activity. , 2004, Chemical reviews.

[95]  W. Denny,et al.  Novel angular benzophenazines: dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents. , 2002, Journal of medicinal chemistry.

[96]  S. Heeb,et al.  Regulatory roles of the GacS/GacA two-component system in plant-associated and other gram-negative bacteria. , 2001, Molecular plant-microbe interactions : MPMI.

[97]  L. Thomashow,et al.  Functional Analysis of Genes for Biosynthesis of Pyocyanin and Phenazine-1-Carboxamide from Pseudomonas aeruginosa PAO1 , 2001, Journal of bacteriology.

[98]  L. Thomashow,et al.  Phenazine Biosynthesis in Pseudomonas fluorescens: Branchpoint from the Primary Shikimate Biosynthetic Pathway and Role of Phenazine-1,6-dicarboxylic Acid , 2001 .

[99]  J. Thomas-Oates,et al.  Introduction of the phzH gene of Pseudomonas chlororaphis PCL1391 extends the range of biocontrol ability of phenazine-1-carboxylic acid-producing Pseudomonas spp. strains. , 2001, Molecular plant-microbe interactions : MPMI.

[100]  L. Thomashow,et al.  phzO, a Gene for Biosynthesis of 2-Hydroxylated Phenazine Compounds in Pseudomonas aureofaciens 30-84 , 2001, Journal of bacteriology.

[101]  G. Taylor,et al.  Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth. , 1999, Journal of clinical pathology.

[102]  D. Wood,et al.  Homoserine lactone-mediated gene regulation in plant-associated bacteria. , 1998, Annual review of phytopathology.

[103]  L. Pierson,et al.  Phenazine antibiotic production in Pseudomonas aureofaciens: role in rhizosphere ecology and pathogen suppression , 1996 .

[104]  H. Kawai,et al.  Phenazoviridin, a novel free radical scavenger from Streptomyces sp. Taxonomy, fermentation, isolation, structure elucidation and biological properties. , 1993, The Journal of antibiotics.

[105]  U. Hollstein,et al.  Interaction of phenazines with polydeoxyribonucleotides. , 1971, Biochemistry.