An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by

Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence....
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Robinson, Jonathan L. [verfasserIn] Jaslove, Jacob M. [verfasserIn] Murawski, Allison M. [verfasserIn] Fazen, Christopher H. [verfasserIn] Brynildsen, Mark P. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification

Übergeordnetes Werk:	Enthalten in: Metabolic engineering - Orlando, Fla. : Academic Press, 1999, 41, Seite 67-81
Übergeordnetes Werk:	volume:41 ; pages:67-81

DOI / URN:	10.1016/j.ymben.2017.03.006

Katalog-ID:	ELV007740808

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245	1	0	\|a An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
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520			\|a Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.
650		4	\|a Metabolic cycle
650		4	\|a Kinetic model
650		4	\|a Oscillations
650		4	\|a NO reductase
650		4	\|a Fhp
650		4	\|a Denitrification
700	1		\|a Jaslove, Jacob M. \|e verfasserin \|4 aut
700	1		\|a Murawski, Allison M. \|e verfasserin \|4 aut
700	1		\|a Fazen, Christopher H. \|e verfasserin \|4 aut
700	1		\|a Brynildsen, Mark P. \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t Metabolic engineering \|d Orlando, Fla. : Academic Press, 1999 \|g 41, Seite 67-81 \|h Online-Ressource \|w (DE-627)267838808 \|w (DE-600)1471017-1 \|w (DE-576)110350340 \|x 1096-7184 \|7 nnns
773	1	8	\|g volume:41 \|g pages:67-81
912			\|a GBV_USEFLAG_U
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912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_32
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
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912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_165
912			\|a GBV_ILN_224
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
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912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2070
912			\|a GBV_ILN_2086
912			\|a GBV_ILN_2098
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2116
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2119
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2144
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2188
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
936	b	k	\|a 42.17 \|j Allgemeine Physiologie \|x Biologie
936	b	k	\|a 42.15 \|j Zellbiologie
951			\|a AR
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Indexfelder

author_variant	j l r jl jlr j m j jm jmj a m m am amm c h f ch chf m p b mp mpb
matchkey_str	article:10967184:2017----::nnertdewraayirvashtircxdrdcaervnseao
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bklnumber	42.17 42.15
publishDate	2017
allfields	10.1016/j.ymben.2017.03.006 doi (DE-627)ELV007740808 (ELSEVIER)S1096-7176(17)30095-2 DE-627 ger DE-627 rda eng 610 DE-600 42.17 bkl 42.15 bkl Robinson, Jonathan L. verfasserin aut An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by 2017 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO. Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification Jaslove, Jacob M. verfasserin aut Murawski, Allison M. verfasserin aut Fazen, Christopher H. verfasserin aut Brynildsen, Mark P. verfasserin aut Enthalten in Metabolic engineering Orlando, Fla. : Academic Press, 1999 41, Seite 67-81 Online-Ressource (DE-627)267838808 (DE-600)1471017-1 (DE-576)110350340 1096-7184 nnns volume:41 pages:67-81 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2098 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 42.17 Allgemeine Physiologie Biologie 42.15 Zellbiologie AR 41 67-81
spelling	10.1016/j.ymben.2017.03.006 doi (DE-627)ELV007740808 (ELSEVIER)S1096-7176(17)30095-2 DE-627 ger DE-627 rda eng 610 DE-600 42.17 bkl 42.15 bkl Robinson, Jonathan L. verfasserin aut An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by 2017 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO. Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification Jaslove, Jacob M. verfasserin aut Murawski, Allison M. verfasserin aut Fazen, Christopher H. verfasserin aut Brynildsen, Mark P. verfasserin aut Enthalten in Metabolic engineering Orlando, Fla. : Academic Press, 1999 41, Seite 67-81 Online-Ressource (DE-627)267838808 (DE-600)1471017-1 (DE-576)110350340 1096-7184 nnns volume:41 pages:67-81 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2098 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 42.17 Allgemeine Physiologie Biologie 42.15 Zellbiologie AR 41 67-81
allfields_unstemmed	10.1016/j.ymben.2017.03.006 doi (DE-627)ELV007740808 (ELSEVIER)S1096-7176(17)30095-2 DE-627 ger DE-627 rda eng 610 DE-600 42.17 bkl 42.15 bkl Robinson, Jonathan L. verfasserin aut An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by 2017 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO. Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification Jaslove, Jacob M. verfasserin aut Murawski, Allison M. verfasserin aut Fazen, Christopher H. verfasserin aut Brynildsen, Mark P. verfasserin aut Enthalten in Metabolic engineering Orlando, Fla. : Academic Press, 1999 41, Seite 67-81 Online-Ressource (DE-627)267838808 (DE-600)1471017-1 (DE-576)110350340 1096-7184 nnns volume:41 pages:67-81 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2098 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 42.17 Allgemeine Physiologie Biologie 42.15 Zellbiologie AR 41 67-81
allfieldsGer	10.1016/j.ymben.2017.03.006 doi (DE-627)ELV007740808 (ELSEVIER)S1096-7176(17)30095-2 DE-627 ger DE-627 rda eng 610 DE-600 42.17 bkl 42.15 bkl Robinson, Jonathan L. verfasserin aut An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by 2017 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO. Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification Jaslove, Jacob M. verfasserin aut Murawski, Allison M. verfasserin aut Fazen, Christopher H. verfasserin aut Brynildsen, Mark P. verfasserin aut Enthalten in Metabolic engineering Orlando, Fla. : Academic Press, 1999 41, Seite 67-81 Online-Ressource (DE-627)267838808 (DE-600)1471017-1 (DE-576)110350340 1096-7184 nnns volume:41 pages:67-81 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2098 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 42.17 Allgemeine Physiologie Biologie 42.15 Zellbiologie AR 41 67-81
allfieldsSound	10.1016/j.ymben.2017.03.006 doi (DE-627)ELV007740808 (ELSEVIER)S1096-7176(17)30095-2 DE-627 ger DE-627 rda eng 610 DE-600 42.17 bkl 42.15 bkl Robinson, Jonathan L. verfasserin aut An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by 2017 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO. Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification Jaslove, Jacob M. verfasserin aut Murawski, Allison M. verfasserin aut Fazen, Christopher H. verfasserin aut Brynildsen, Mark P. verfasserin aut Enthalten in Metabolic engineering Orlando, Fla. : Academic Press, 1999 41, Seite 67-81 Online-Ressource (DE-627)267838808 (DE-600)1471017-1 (DE-576)110350340 1096-7184 nnns volume:41 pages:67-81 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_165 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2098 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 42.17 Allgemeine Physiologie Biologie 42.15 Zellbiologie AR 41 67-81
language	English
source	Enthalten in Metabolic engineering 41, Seite 67-81 volume:41 pages:67-81
sourceStr	Enthalten in Metabolic engineering 41, Seite 67-81 volume:41 pages:67-81
format_phy_str_mv	Article
bklname	Allgemeine Physiologie Zellbiologie
institution	findex.gbv.de
topic_facet	Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification
dewey-raw	610
isfreeaccess_bool	false
container_title	Metabolic engineering
authorswithroles_txt_mv	Robinson, Jonathan L. @@aut@@ Jaslove, Jacob M. @@aut@@ Murawski, Allison M. @@aut@@ Fazen, Christopher H. @@aut@@ Brynildsen, Mark P. @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	267838808
dewey-sort	3610
id	ELV007740808
language_de	englisch
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author	Robinson, Jonathan L.
spellingShingle	Robinson, Jonathan L. ddc 610 bkl 42.17 bkl 42.15 misc Metabolic cycle misc Kinetic model misc Oscillations misc NO reductase misc Fhp misc Denitrification An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
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topic_title	610 DE-600 42.17 bkl 42.15 bkl An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by Metabolic cycle Kinetic model Oscillations NO reductase Fhp Denitrification
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title	An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
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title_full	An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
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author_browse	Robinson, Jonathan L. Jaslove, Jacob M. Murawski, Allison M. Fazen, Christopher H. Brynildsen, Mark P.
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title_sort	an integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
title_auth	An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
abstract	Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.
abstractGer	Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.
abstract_unstemmed	Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.
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title_short	An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by
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author2	Jaslove, Jacob M. Murawski, Allison M. Fazen, Christopher H. Brynildsen, Mark P.
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up_date	2024-07-06T17:17:52.658Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV007740808</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230524153825.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230507s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ymben.2017.03.006</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV007740808</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S1096-7176(17)30095-2</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">42.17</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">42.15</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Robinson, Jonathan L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2 −) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3 −) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3 −→NO2 −→NO). Deeper understanding of NO metabolism in P. aeruginosa will increase knowledge of its pathogenesis, and computational models have proven to be useful tools for the quantitative dissection of NO biochemical networks. Here we developed such a model for P. aeruginosa and confirmed its predictive accuracy with measurements of NO, O2, NO2 −, and NO3 − in mutant cultures devoid of Fhp or NorCB (NO reductase) activity. Using the model, we assessed whether NO was metabolically cycled in aerobic P. aeruginosa cultures. Calculated fluxes indicated a bottleneck at NO3 −, which was relieved upon O2 depletion. As cell growth depleted dissolved O2 levels, NO3 − was converted to NO2 − at near-stoichiometric levels, whereas NO2 − consumption did not coincide with NO or NO3 − accumulation. Assimilatory NO2 − reductase (NirBD) or NorCB activity could have prevented NO cycling, and experiments with ΔnirB, ΔnirS, and ΔnorC showed that NorCB was responsible for loss of flux from the cycle. Collectively, this work provides a computational tool to analyze NO metabolism in P. aeruginosa, and establishes that P. aeruginosa use NorCB to prevent metabolic cycling of NO.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Metabolic cycle</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kinetic model</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Oscillations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">NO reductase</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Fhp</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Denitrification</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jaslove, Jacob M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Murawski, Allison M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fazen, Christopher H.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Brynildsen, Mark P.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Metabolic engineering</subfield><subfield code="d">Orlando, Fla. : Academic Press, 1999</subfield><subfield code="g">41, Seite 67-81</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)267838808</subfield><subfield code="w">(DE-600)1471017-1</subfield><subfield code="w">(DE-576)110350340</subfield><subfield code="x">1096-7184</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" 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An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by

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