ライフサイエンスコーパス: phenazine

1 hexanoic acid; dppz = dipyrido[3,2-a:2',3'-c]phenazine).

2 e production of virulence factors (including phenazines).

3 ys previously unknown coordination modes for phenazine.

4 he survival effect is specific to endogenous phenazines.

5 es colorful, redox-active antibiotics called phenazines.

6 fluorescent pseudomonads produce and secrete phenazines.

7 CAM-1 and IL-8 increases in response to both phenazines.

8 nthesis of highly functionalized benzo fused phenazines.

9 hes it from other well-studied P. aeruginosa phenazines.

10 r type N,N'-disubstituted-dihydrodibenzo[a,c]phenazines.

11 our distinct redox-active metabolites called phenazines.

12 ido[3,2-alpha: 2',3'-c:3'',2''-h:2''',3'''-j]phenazine) (1), was studied using cyclic voltammetry wit

13 aeruginosa, pyocyanin (Py) and its precursor phenazine-1- carboxylic acid (PCA), and two chemically s

14 Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G-prote

15 tified and was shown to control synthesis of phenazine-1-carboxamide from PCA in P. aeruginosa PAO1.

16 of PCA to pyocyanin, 1-hydroxyphenazine, and phenazine-1-carboxamide.

17 Pseudomonas fluorescens 2-79, which produces phenazine-1-carboxylate, is preceded by two genes, phzR

18 omplex would prevent the release of 5-methyl-phenazine-1-carboxylate, the putative intermediate, and

19 es including the recently described 5-methyl-phenazine-1-carboxylic acid (5MPCA), which exhibits a no

20 P. chlororaphis produces mainly two PZs, phenazine-1-carboxylic acid (PCA) and 2-hydroxy-PCA (2-O

21 f purified PhzF, -A, -B, and -G confirm that phenazine-1-carboxylic acid (PCA) is readily produced fr

22 phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony,

23 Here we report the ability of phenazine-1-carboxylic acid (PCA), a common phenazine ma

24 monstrated that the precursor for pyocyanin, phenazine-1-carboxylic acid (PCA), increases oxidant for

25 of PQS, likely induces the production of the phenazine-1-carboxylic acid (PCA), which in turn acts vi

26 ficient for production of a single compound, phenazine-1-carboxylic acid (PCA).

27 enazine from the common phenazine metabolite phenazine-1-carboxylic acid (PCA).

28 the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA).

29 n of the endogenous phenazines pyocyanin and phenazine-1-carboxylic acid in both cytosolic and membra

30 Phenazine-1-carboxylic acid, the initial phenazine forme

31 s of proteins that catalyze the synthesis of phenazine-1-carboxylic acid, the precursor for several p

32 Phenazine-1-carboxylic acid, the precursor to the bioact

33 y from the dipyrido[3,2-a:2',3'-c]-benzo[3,4]phenazine-11,16-quinone (NqPhen) ligand starting materia

34 has been demonstrated for 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)-me

35 xic agents, exemplified by 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)-me

36 Halogenated phenazine 14 proved to be the most potent biofilm-eradic

37 In alfalfa, treating roots with 200 microm phenazine, 2,4-diacetylphloroglucinol, or zearalenone in

38 1 (a 1:1 mixture of 9-hydroxy- and 6-hydroxy-phenazine-2-carobxylic acids), designed to recognize 1-h

39 phthalenes 3, and 5-arylthio-/5-aminobenzo[a]phenazines 4 in very good isolated yields.

40 inoxaline) (3), dppz (dipyrido[3,2-a:2',3'-c]phenazine) (4), dppn (benzo[i]dipyrido[3,2-a:2',3'-c]phe

41 e) (4), dppn (benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) (5), and dap (4,7-dihydrodibenzo[de,gh][1,10]

42 qdppz = naphtho[2,3-a]dipyrido[3,2-h:2',3'-f]phenazine-5,18-dione), with lambdamax = 450 nm.

43 zi](3+) (bpy, 2,2'-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a st

44 f diazapentacenes (5,14-diethynyldibenzo[b,i]phenazine, 6,13-diethynylnaphtho[2,3-b]phenazine) and te

45 onizing fluorescent Pseudomonas spp. produce phenazines, a class of antifungal metabolites that can p

46 udomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular

47 Following evidence that phenazines act as virulence factors in the opportunistic

48 Phenazines also enhance survival of 30-84 within the whe

49 ynthesis of this metabolite and a variety of phenazine analogues should be developed.

50 [(C5Me5)2SmH]2 reduces phenazine and anthracene to make [(C5Me5)2Sm]2(mu-eta(3)

51 y isolate two organic crystalline compounds, phenazine and caffeine, from their suspension in 1,4-dio

52 Further unimolecular rearrangements afford phenazine and carbazole.

53 Production of phenazine and phloroglucinol antibiotics, as examples, a

54 diates for the preparation of polyfunctional phenazines and extended polyheteroacenes.

55 Finally, we show that phenazines and other P. aeruginosa factors required for

56 We have synthesized a series of ethynylated phenazines and their bis-triazolyl cycloadducts to serve

57 o[b,i]phenazine, 6,13-diethynylnaphtho[2,3-b]phenazine) and tetraazapentacenes (7,12-diethynylbenzo[g

58 resulted in the increased production of the phenazine antibiotic pyocyanin and the siderophore pyove

59 ntity to PhzF, a bacterial DAHPS involved in phenazine antibiotic synthesis.

60 ystem to positively regulate biosynthesis of phenazine antibiotics that contribute to its association

61 This strain produces three phenazine antibiotics which suppress take-all disease of

62 eofaciens 30-84 is due (at least in part) to phenazine antibiotics whose synthesis is regulated by N-

63 g compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux p

64 ted to control the appropriate expression of phenazine antibiotics.

65 w that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for

66 Phenazines are a class of redox-active molecules produce

67 Phenazines are antimicrobial compounds that provide Pseu

68 In this work, the thienyl-substituted phenazines are investigated in more detail by time-resol

69 Phenazines are well known for their toxicity against non

70 primary aromatic amines produce substituted phenazines as major products, N-phenyl-o-phenylenediamin

71 Our results implicate phenazines as signalling molecules in both P. aeruginosa

72 stimulates matrix production, in response to phenazine availability.

73 f action, the biochemistry and mechanisms of phenazine biosynthesis are not well resolved.

74 contributions of these redundant operons to phenazine biosynthesis have not been evaluated.

75 The disruption of phenazine biosynthesis led to broad changes in specializ

76 yotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family.

77 an remodeling, uptake of phosphate and iron, phenazine biosynthesis, and other processes were identif

78 In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin i

79 A crystal structure of PhzF, a key enzyme in phenazine biosynthesis, solved by molecular replacement.

80 aeruginosa is an isochorismatase involved in phenazine biosynthesis.

81 expression of the phnAB operon, involved in phenazine biosynthesis.

82 phnB) had previously been assumed to encode phenazine biosynthetic functions.

83 low, inactivation of the rpeA gene enhanced phenazine biosynthetic gene expression and increased phe

84 lations with fluorescent reporter imaging of phenazine biosynthetic gene expression.

85 Furthermore, RpeA functioned to block phenazine biosynthetic gene transcription in minimal med

86 oson insertion into a Pseudomonas aeruginosa phenazine biosynthetic gene, phzF2.

87 Two seven-gene phenazine biosynthetic loci were cloned from Pseudomonas

88 Despite the fact that the phenazine biosynthetic locus is highly conserved among f

89 Disruption of phzI reduced expression of the phenazine biosynthetic operon 1,000-fold in the wheat rh

90 Expression of the phenazine biosynthetic operon is controlled by the phzR/

91 E2F2G2, are homologous to previously studied phenazine biosynthetic operons from Pseudomonas fluoresc

92 vided into those with defects in the primary phenazine biosynthetic pathway and those with more pleio

93 hranilic acid, which is then utilized in the phenazine biosynthetic pathway.

94 electrophoresis showed increased amounts of phenazine biosynthetic proteins in FRD1 biofilms and in

95 s for further structural variations of these phenazine building blocks.

96 ss or limitation stimulate the production of phenazines, but little is known of the molecular details

97 xtracellular redox-active molecules, such as phenazines, can broaden the metabolic versatility of mic

98 f this new series of substituted 8,9-benzo[a]phenazine carboxamide systems are described.

99 acene (1,4,8,11-tetrachloroquinoxalino[2,3-b]phenazine) carrying its chlorine atoms in the peri-posit

100 The phenazine chromophore of MLN944 is very well stacked wit

101 ters and experimentally validate a divergent phenazine cluster with potential new chemical structure

102 Phenazine compounds represent a large class of bacterial

103 ., individual strains differ in the range of phenazine compounds they produce.

104 Phenazine conidiation signaling was conserved in the gen

105 Phenazine-containing spent culture supernatants of Pseud

106 These studies suggest that P. aeruginosa phenazines coordinately up-regulate chemokines (IL-8) an

107 These phenazine cycloadducts exhibit a selective affinity for

108 ntly decreased metal-binding activity of the phenazine cycloadducts.

109 Complex 1 reduces phenazine, cyclooctatetraene, anthracene, and azobenzene

110 uginosa produces pyocyanin, a blue-pigmented phenazine derivative, which is known to play a role in v

111 sium diisopropylamide afforded alkyl-shifted phenazine derivatives 5a/5b, rather than the expected 9-

112 Several of the active phenazine derivatives displayed IC values vs QR1 inducti

113 The phenazine derivatives were isolated in 78-98% yield depe

114 lo-2,2-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]phenazine derivatives with good to excellent yields.

115 o monohydrodeaminate the 2,3-di(methylamino) phenazine derivatives, which allows for further structur

116 1-carboxylic acid, the precursor for several phenazine derivatives.

117 n coculture biofilms, Pseudomonas aeruginosa phenazine-derived metabolites differentially modulated A

118 ppz and the cation ethylene-bipyridyldiylium-phenazine dinitrate [[1][(PF(6))(2)]] have been obtained

119 soluble derivative of dipyrido[3,2-a:2',3'-c]phenazine (dppz) is reported.

120 The phenazine dyes undergo a quasi-reversible reduction at a

121 Together, our results suggest that phenazines enable maintenance of the proton-motive force

122 Moreover, phenazines enhanced cytokine-dependent increases in IL-8

123 n analogs, phenazine methosulfate (PMS+) and phenazine ethosulfate (PES+).

124 ore, 1e(-) oxidation of the DMS species with phenazine ethosulfate yields a Mo(V) form without an -OH

125 responses to oxidative stress suggests that phenazines exert their toxic effects on C. elegans throu

126 y, the N,N'-disubstituted-dihydrodibenzo[a,c]phenazines exhibit multiple emissions, which can be wide

127 Although phenazines exist in many forms, the best studied is pyoc

128 results demonstrate that HHL is required for phenazine expression in situ and is an effective interpo

129 Here we show that phenazine-facilitated electron transfer to poised-potent

130 Phenazine-1-carboxylic acid, the initial phenazine formed, is converted to pyocyanin in two steps

131 a level that was sufficient for induction of phenazine gene expression in rich medium.

132 produced the endogenous HHL signal restored phenazine gene expression in the phzI mutant to wild-typ

133 sporulation (conidiation) along a decreasing phenazine gradient.

134 An axial chiral tetrachlorinated bisbenzo[a]phenazine has been discovered that undergoes an alkane-i

135 An example of this is the effect that phenazines have on signaling and community development f

136 ity relationships of a series of halogenated phenazines (HP) inspired by 2-bromo-1-hydroxyphenazine 1

137 We report a series of halogenated phenazines (HP), inspired by marine antibiotic 1, that t

138 lar synthesis of a library of 20 halogenated phenazines (HP), utilizing the Wohl-Aue reaction, that t

139 The phenazines include upward of 50 pigmented, heterocyclic

140 Pseudomonas aeruginosa produces several phenazines including the recently described 5-methyl-phe

141 Phenazines, including pyocyanin and iodonin, are biologi

142 ion of N,N'-disubstituted-dihydrodibenzo[a,c]phenazines, intramolecular charge-transfer takes place,

143 rapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) is luminescent when bound to DNA and in organ

144 etion of pyocyanin, the best-studied natural phenazine, is responsible for the bluish tint of sputum

145 boxylic acid, the precursor to the bioactive phenazines, is synthesized from chorismic acid by enzyme

146 romatic pdppz ([2,3-h]dipyrido[3,2-a:2',3'-c]phenazine) ligand and exhibits photoactivity through inc

147 phenazine-1-carboxylic acid (PCA), a common phenazine made by all phenazine-producing pseudomonads,

148 is by oxidizing NADH, our work suggests that phenazines may substitute for NAD(+) in LpdG and other e

149 ventions are equally effective in inhibiting phenazine-mediated proinflammatory effects.

150 -PCA) and 2-hydroxyphenazine from the common phenazine metabolite phenazine-1-carboxylic acid (PCA).

151 ous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa

152 terest is the observation that P. aeruginosa phenazine metabolites were converted by A. fumigatus int

153 Phenazine methosulfate (PMS) was used as a mediator whic

154 nm in the presence of a fast electron donor (phenazine methosulfate (PMS)).

155 redox dye tetranitroblue tetrazolium (TNBT), phenazine methosulfate (PMS), NAD(+), and 6-phosphogluco

156 wo chemically synthesized pyocyanin analogs, phenazine methosulfate (PMS+) and phenazine ethosulfate

157 rated by the electron donor system ascorbate-phenazine methosulfate but not by the electron donor sys

158 oxide generation, either through addition of phenazine methosulfate or by deletion of sodA and sodB,

159 Treatment with the redox cycling agents phenazine methosulfate or plumbagin was accompanied by r

160 th the cell membrane and exhibited D-lactate:phenazine methosulfate reductase activity and oxidized D

161 ransfer from ISP reduced with ascorbate plus phenazine methosulfate to cytochrome b was studied in SM

162 amide adenine dinucleotide phosphate (NADP), phenazine methosulfate, and iodonitrotetrazolium violet,

163 Upon reconstitution of the pmf with phenazine methosulfate, glucose, and oxygen, fluorescenc

164 cs and to the superoxide-generating compound phenazine methosulfate.

165 m was dependent on energization by ascorbate-phenazine methosulfate.

166 ystem (they used a chemical system, NADH and phenazine methosulfate; N/PMS).

167 ungal mechanisms of 5MPCA using its analogue phenazine methosulphate (PMS).

168 were more sensitive to hydrogen peroxide and phenazine methosulphate, and some PAI mutant strains als

169 dative stress, it was shown that juglone and phenazine methylsulfate are potentially toxic to the par

170 ed by tert-butyl-hydroperoxide, juglone, and phenazine methylsulfate with IC(50) in the nanomolar ran

171 Others of the pleiotropic phenazine-minus mutations appear to inactivate novel com

172 A third phenazine-modifying gene, phzH, which has a homologue in

173 in is mediated in P. aeruginosa by two novel phenazine-modifying genes, phzM and phzS, which encode p

174 of the pi-delocalization over the benzo[a,c]phenazines moiety.

175 For example, the phenazine molecules exhibited absorption peaks between 4

176 ne water molecule is directly located on one phenazine N atom in the Delta-enantiomer only.

177 ions is achieved through coordination to the phenazine nitrogen atom and the triazole ring.

178 Functional studies of phenazine-nonproducing strains of fluorescent pseudomona

179 isms to produce multiple phenazines or novel phenazines not previously described.

180 Pyocyanin addition to a phenazine-null mutant also decreased intracellular NADH

181 novel gene located downstream from the core phenazine operon that encodes a 55-kDa aromatic monooxyg

182 to manipulate organisms to produce multiple phenazines or novel phenazines not previously described.

183 olysaccharide, phospholipases, exoproteases, phenazines, outer membrane vesicles, type III secreted e

184 prior studies have focused on extracellular phenazine oxidation by oxygen and iron, here we report a

185 anin is produced from chorismic acid via the phenazine pathway, nine proteins encoded by a gene clust

186 Phenazines perform diverse roles in P. aeruginosa physio

187 The production of phenazine (Ph) antibiotics in Pseudomonas aureofaciens (

188 two-component cocrystal by grinding together phenazine (phen) and mesaconic acid (mes).

189 Mo(PMe(3))(6) reacts with phenazine (PhzH) to give (eta(6)-C(6)-PhzH)Mo(PMe(3))(3)

190 mutants exhibiting reduced production of the phenazine poison pyocyanin were isolated following trans

191 and 3,11-di(10H-phenoxazin-10-yl)dibenzo[a,j]phenazine (POZ-DBPHZ) in two different hosts.

192 Pyocyanin is a biologically active phenazine produced by the human pathogen Pseudomonas aer

193 diversity, frequency and ecological roles of phenazines produced by fluorescent Pseudomonas spp.

194 s the stage for improving the performance of phenazine producers used as biological control agents fo

195 re well known for their toxicity against non-phenazine-producing organisms, which allows them to serv

196 c acid (PCA), a common phenazine made by all phenazine-producing pseudomonads, to help P. aeruginosa

197 Knowledge of the genes responsible for phenazine product specificity could ultimately reveal wa

198 e biosynthetic gene expression and increased phenazine production but did not increase quorum sensing

199 Coincident with phenazine production during batch culture growth, Fe(II)

200 To date, no negative regulators of phenazine production have been identified, nor has the r

201 We characterize phenazine production in both wild-type and mutant Pseudo

202 In minimal medium where phenazine production is very low, inactivation of the rp

203 Our results suggest that phenazine production modulates RmcA activity such that t

204 lysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1

205 though phz2 showed a greater contribution to phenazine production.

206 , and phz2 was responsible for virtually all phenazine production.

207 e wild-type strain and a mutant defective in phenazine production.

208 the quorum sensor PhzR was not required for phenazine production.

209 pulation that renders the cells incapable of phenazine production.

210 The phenazine pyocyanin (and the closely related molecule pa

211 Unlike PCA, the phenazine pyocyanin (PYO) can facilitate biofilm formati

212 biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxyli

213 quantitative RT-PCR, we demonstrate that the phenazine pyocyanin elicits the upregulation of genes/op

214 gnized virulence factors is the redox-active phenazine pyocyanin.

215 hat catalyze the reduction of the endogenous phenazines pyocyanin and phenazine-1-carboxylic acid in

216 secretes copious amounts of the redox-active phenazine, pyocyanin (PCN), during cystic fibrosis lung

217 The production of phenazines (PZs) by strain 30-84 is the primary mechanis

218 s readily synthesized by condensation of the phenazine quinone with the corresponding diammine comple

219 ical shift correlated with the production of phenazine radicals and concomitant reactive oxygen speci

220 Here, we demonstrate that phenazine redox cycling enables P. aeruginosa to oxidize

221 oxygen species (ROS) production generated by phenazine redox cycling.

222 which is available from the atmosphere, and phenazines, redox-active antibiotics produced by the bac

223 ine reduction in vitro, suggesting that most phenazine reduction derives from these enzymes.

224 or reductants and catalysts of intracellular phenazine reduction in Pseudomonas aeruginosa Enzymatic

225 , diphenyleneiodonium, effectively inhibited phenazine reduction in vitro, suggesting that most phena

226 te dehydrogenase complexes directly catalyze phenazine reduction with pyruvate or alpha-ketoglutarate

227 Although repression plays a critical role in phenazine regulation, the rpeA mutation could not bypass

228 imines and azobenzenes to give acridines and phenazines, respectively.

229 ilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent in

230 tion in the DNA complex, with the N10 on the phenazine ring protonated at pH 7.

231 The basic, tricyclic phenazine ring system is synthesized in a series of poor

232 rating a novel binding mode in which the two phenazine rings bis-intercalate at the 5'-TpG site, with

233 estigated under aerobic conditions using two phenazine secondary metabolites excreted by P. aeruginos

234 nt that lacks P-glycoproteins, we identified phenazines, secreted P. aeruginosa pigments, as one of t

235 tic pathogen Pseudomonas aeruginosa produces phenazines, small molecules that act as alternate electr

236 genes, phzM and phzS, which encode putative phenazine-specific methyltransferase and flavin-containi

237 Many of the biological functions of phenazines, such as mediating signaling, iron acquisitio

238 s of chlorinated carbazole, phenoxazine, and phenazine suggests the formation of these species by ele

239 In contrast to the notion that phenazines support intracellular redox homeostasis by ox

240 Previously, we reported that endogenous phenazines support the anaerobic survival of P. aerugino

241 he genetics, biochemistry, and regulation of phenazine synthesis, as well as the mode of action and f

242 Since 5MPCA was more toxic than other phenazines that are not modified, such as pyocyanin, we

243 monads produce redox active compounds called phenazines that function in a variety of biological proc

244 Both complexes transfer electrons to phenazines through the common subunit dihydrolipoamide d

245 henanthroline, dppz = dipyrido[3,2-a:2'.3'-c]phenazine), to study aggregation of alpha-synuclein (alp

246 Expression profiling showed phenazine treatment induced a NapA-dependent response of

247 aphenanthrene, dppz = dipyrido[3,2-a:2',3'-c]phenazine), undergoes a partial transition from an A/B h

248 les, the electron spins are localized on the phenazine unit, in which the sulfur atom of the fused th

249 in-like species, carbazole, phenoxazine, and phenazine via unimolecular rearrangements of diphenylami

250 idine, dppn = benzo[i]dipyrido[3,2-a;2',3'-c]phenazine) was synthesized and characterized in an effor

251 le to co-crystallize LpdG with an endogenous phenazine, we report its X-ray crystal structure in the

252 Phenazines were first noted in the scientific literature

253 Numerous phenazines were subsequently prepared and evaluated as i

254 quinoxaline, 6,13-diethynylquinoxalino[2,3-b]phenazine) were reduced to their radical anions and dian

255 ces colorful redox-active metabolites called phenazines, which underpin biofilm development, virulenc

256 somer (2,3,9,10-tetrachloroquinoxalino[2,3-b]phenazine, with the chlorine atoms in the east and west

257 at room temperature for thienyl-substituted phenazines without any heavy metals ( Ratzke et al.