Phenazine-1-carboxylic acid is negatively regulated and pyoluteorin positively regulated by gacA in Pseudomonas sp. M18

Ge, Yihe; Huang, Xianqing; Wang, Sulian; Zhang, Xuehong; Xu, Yuquan

doi:10.1016/j.femsle.2004.06.028

Cited by 37 publications

(52 citation statements)

References 41 publications

(42 reference statements)

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“…S1 in the supplemental material). The transcriptome results were also confirmed by our previous report that the GacS/GacA two-component system (TCS) activated Plt biosynthesis and its operon expression and exerted strong downregulation on PCA biosynthesis and phz operon expression in M18 (10).…”

Section: Resultssupporting

confidence: 85%

“…2C). This further confirms our previous result (10) and is also consistent with results reported for P. protegens Pf-5 (23). Two homologous phz gene clusters revealed an approximately 2-fold increase at the transcript level in the gacA mutant compared with their expression in M18.…”

Section: Gaca Acts As a Central Regulator Of Secondary Metabolismsupporting

confidence: 94%

“…A temperature of 37°C instead of 28°C is more favorable for phzM expression and PYO biosynthesis (14). Apart from the different and strong transcriptional regulation from all three P. aeruginosa quorum-sensing (QS) systems (Las, Rhl, and PQS) (11,12,15), antibiotic biosynthesis in the M18 strain is also subject to posttranscriptional regulation from the sRNA chaperone Hfq (16) and the Gac/Rsm signal transduction cascade (10,17).…”

mentioning

confidence: 99%

“…Moreover, one section of the activating pathway driven by Gac may be mediated by PltR (13). Intriguingly, the Gac system exerts strong downregulation on PCA biosynthesis through an uncharacterized mechanism (10).…”

mentioning

confidence: 99%

“…During the long-term adaptation to rhizosphere environmental pressure, P. aeruginosa strain M18 may have evolved a unique set of secondary metabolic profiles involved in antibiotic biosynthesis and numerous corresponding global regulatory mechanisms, including Gac/Rsm (10,17) and QS (11,12,15). The complex and diverse regulatory mechanisms of the Gac system in M18 urged us to analyze the global pattern of genomic expression of the gacA mutant and to further explore the importance of the Gac system to overall physiology and metabolism and the regulatory network of the Gac system.…”

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confidence: 99%

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Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

et al. 2013

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The rhizobacterium Pseudomonas aeruginosa M18 can produce a broad spectrum of secondary metabolites, including the antibiotics pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA), hydrogen cyanide, and the siderophores pyoverdine and pyochelin. The antibiotic biosynthesis of M18 is coordinately controlled by multiple distinct regulatory pathways, of which the GacS/GacA system activates Plt biosynthesis but strongly downregulates PCA biosynthesis. Here, we investigated the global influence of a gacA mutation on the M18 transcriptome and related metabolic and physiological processes. Transcriptome profiling revealed that the transcript levels of 839 genes, which account for approximately 15% of the annotated genes in the M18 genome, were significantly influenced by the gacA mutation during the early stationary growth phase of M18. Most secondary metabolic gene clusters, such as pvd, pch, plt, amb, and hcn, were activated by GacA. The GacA regulon also included genes encoding extracellular enzymes and cytochrome oxidases. Interestingly, the primary metabolism involved in the assimilation and metabolism of phosphorus, sulfur, and nitrogen sources was also notably regulated by GacA. Another important category of the GacA regulon was secretion systems, including H1, H2, and H3 (type VI secretion systems [T6SSs]), Hxc (T2SS), and Has and Apr (T1SSs), and CupE and Tad pili. More remarkably, GacA inhibited swimming, swarming, and twitching motilities. Taken together, the Gac-initiated global regulation, which was mostly mediated through multiple regulatory systems or factors, was mainly involved in secondary and primary metabolism, secretion systems, motility, etc., contributing to ecological or nutritional competence, ion homeostasis, and biocontrol in M18. P seudomonas aeruginosa M18 is a unique and well-characterized biocontrol rhizobacterium showing a strong antifungal capability (1, 2). It can produce a diverse range of secondary metabolites, including antibiotics, siderophores, and extracellular enzymes, such as phenazine-1-carboxylic acid (PCA), pyoluteorin (Plt), hydrogen cyanide (HCN), L-2-amino-4-methoxy-trans-3-butenoic acid (AMB), pyoverdine, pyochelin, and alkaline protease (1, 2). In contrast to primary metabolism, which is essential for maintaining normal physiological processes, secondary metabolism is not absolutely required for bacterial survival but contributes to ecological and nutritional competence. AMB, a potent antibiotic and toxin, has received little attention (3). The antibiotics PCA and Plt mainly contribute to the strong antifungal capacity of the M18 strain. In the M18 genome, two copies of phenazine biosynthetic operons are highly homologous to each other and to those in P. aeruginosa PAO1 (2, 4). However, the Plt biosynthetic structural, regulatory, and transport gene cluster is conserved in gene organization and size between P. aeruginosa M18 and P. protegens Pf-5 (previously called P. fluorescens) but displays a certain level of difference in the nucleotide sequence, especially the n...

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Section: Resultssupporting

confidence: 85%

Section: Gaca Acts As a Central Regulator Of Secondary Metabolismsupporting

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

et al. 2013

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Medium factor optimization and fermentation kinetics for phenazine‐1‐carboxylic acid production by Pseudomonas sp. M18G

Zhang

2007

Biotech & Bioengineering

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We investigated the production of biofungicide phenazine-1-carboxlic (PCA) by Pseudomonas sp. M18G, a gacA-deficient mutant of M18 for PCA high-production. Glucose was chosen as the optimal carbon source and soy peptone as the nitrogen source. A Plackett-Burman design revealed that glucose, soy peptone and NaCl were the most significant factors in PCA fermentation. Response surface methodology (RSM) and artificial neural network (ANN) models involving the significant factors were developed using common data. The prediction accuracy of ANN was slightly higher compared to RSM. The genetic algorithm (GA) was used to search the optimal input space of the trained ANN model and find the corresponding PCA yield. The optimum composition was found to be: glucose 34.3 g L(-1), soy peptone 43.2 g L(-1), NaCl 5.7 g L(-1), and the predictive maximum PCA yield reached 980.1 microg mL(-1). The optimized medium allowed PCA yield to be increased from 673.3 to 966.7 microg mL(-1) after verification experiment tests. Additionally, PCA fermentation kinetics was investigated. Kinetic models based on the modified Logistic and Luedeking-Piret equations were developed, providing a good description of temporal variations of biomass (X), product (P), and substrate (S) in PCA fermentation.

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Fermentative Production of Bacterial Phenazines

Chincholkar

Patil

Sarode

et al. 2013

Microbial Phenazines

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Phenazines, a nitrogen containing heterocyclic antibiotic biosynthesized by a diverse range of bacteria. Owing its enormous importance as (1) electron shuttles to alternate terminal acceptors in bacteria, (2) modify cellular redox states to modify host response, (3) contributing to biofilm formation and cell signaling, as well as (4) biotechnological applications such as environmental sensor, microbial fuel cell, antitumor, and biocontrol activity attracted attention of scientific community to target phenazine as lead molecule. Similarly, emerging application of phenazines insisted high productivity fermentative process. Current chapter focuses on sources of natural phenazines and impact of nutritional as well as environmental dynamics on fermentative production of phenazine in different bacteria.

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Phenazine-1-carboxylic acid is negatively regulated and pyoluteorin positively regulated by gacA in Pseudomonas sp. M18

Cited by 37 publications

References 41 publications

Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

Medium factor optimization and fermentation kinetics for phenazine‐1‐carboxylic acid production by Pseudomonas sp. M18G

Fermentative Production of Bacterial Phenazines

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