The explosive-degrading cytochrome P450 XplA: Biochemistry, structural features and prospects for bioremediation

Rylott, Elizabeth L.; Jackson, Rosamond G.; Sabbadin, Federico; Seth-Smith, Helena M. B.; Edwards, James; Chong, Chun Shiong; Strand, Stuart E.; Grogan, Gideon; Bruce, Neil C.

doi:10.1016/j.bbapap.2010.07.004

Cited by 55 publications

(36 citation statements)

References 41 publications

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“…Studies using 18 O 2 and H 2 18 O also demonstrated that a labeled oxygen was incorporated into 4-nitro-2,4-diazabutanal product only from H 2 18 O, apparently ruling out redox partnerdependent P450 heme iron-mediated oxygen insertion chemistry from either CYP2B4 or the Rhodococcus (XplA) P450 (25). This conclusion is also consistent with the observation that a phylogenetically conserved cytochrome P450 Ser/Thr residue that participates in oxygen activation is absent in XplA (1,26).…”

supporting

confidence: 75%

“…Recent years have seen recognition of a wider diversity of redox systems driving P450 enzymes, including the well characterized Bacillus megaterium P450 BM3 (CYP102A1) fatty acid hydroxylase, a soluble P450-NADPH-cytochrome P450 reductase fusion enzyme (18), and a sterol demethylase (CYP51) class P450 fused to its cognate ferredoxin, McCYP51FX from Methylococcus capsulatus (19,20). XplA falls into a different class of P450 redox system, with a flavodoxin-like module (N-terminal) fused to the P450 (1,21,22). XplA receives electrons from a NADPH-dependent flavoprotein reductase (XplB) encoded by the xplB gene immediately upstream of xplA on the R. rhodochrous strain 11Y genome (23).…”

mentioning

confidence: 99%

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Unusual Spectroscopic and Ligand Binding Properties of the Cytochrome P450-Flavodoxin Fusion Enzyme XplA

Bui

McLean

Cheesman

et al. 2012

Journal of Biological Chemistry

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supporting

confidence: 75%

mentioning

confidence: 99%

Unusual Spectroscopic and Ligand Binding Properties of the Cytochrome P450-Flavodoxin Fusion Enzyme XplA

Bui

McLean

Cheesman

et al. 2012

Journal of Biological Chemistry

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“…A soluble biotechnologically relevant P450 enzyme from Rhodococcus rhodochrous strain 11Y (XplA) has an FDx module fused to the P450 at its N terminus. XplA receives electrons from an NADPH-dependent flavoprotein reductase (XplB) and catalyzes the reductive degradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine, producing nitrite as a final product (57).…”

Section: P450-redox Partner Fusion Proteinsmentioning

confidence: 99%

Unusual Cytochrome P450 Enzymes and Reactions

Guengerich

Munro

2013

Journal of Biological Chemistry

300

217

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Cytochrome P450 enzymes primarily catalyze mixed-function oxidation reactions, plus some reductions and rearrangements of oxygenated species, e.g. prostaglandins. Most of these reactions can be rationalized in a paradigm involving Compound I, a high-valent iron-oxygen complex (FeO 3؉ ), to explain seemingly unusual reactions, including ring couplings, ring expansion and contraction, and fusion of substrates. Most P450s interact with flavoenzymes or iron-sulfur proteins to receive electrons from NAD(P)H. In some cases, P450s are fused to protein partners. Other P450s catalyze non-redox isomerization reactions. A number of permutations on the P450 theme reveal the diversity of cytochrome P450 form and function.

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“…The products of secondary nitramine degradation are often primary nitramines, similar to NNG. For example, a cytochrome P450 system catalyzes the initial reaction in bacteria that use RDX as the sole source of nitrogen (27)(28)(29)(30)(31)(32)(33). The enzyme cleaves nitro groups from RDX in a pathway that releases nitrite and yields linear nitramine products.…”

Section: N -Nitroglycine ([Nng] Nitraminoacetic Acid) Is a Nitramine mentioning

confidence: 99%

Iron-Dependent Enzyme Catalyzes the Initial Step in Biodegradation of N -Nitroglycine by Variovorax sp. Strain JS1663

Mahan

Zheng

Fida

et al. 2017

Appl Environ Microbiol

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Nitramines are key constituents of most of the explosives currently in use and consequently contaminate soil and groundwater at many military facilities around the world. Toxicity from nitramine contamination poses a health risk to plants and animals. Thus, understanding how nitramines are biodegraded is critical to environmental remediation. The biodegradation of synthetic nitramine compounds such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been studied for decades, but little is known about the catabolism of naturally produced nitramine compounds. In this study, we report the isolation of a soil bacterium, Variovorax sp. strain JS1663, that degrades N-nitroglycine (NNG), a naturally produced nitramine, and the key enzyme involved in its catabolism. Variovorax sp. JS1663 is a Gram-negative, non-sporeforming motile bacterium isolated from activated sludge based on its ability to use NNG as a sole growth substrate under aerobic conditions. A single gene (nnlA) encodes an iron-dependent enzyme that releases nitrite from NNG through a proposed ␤-elimination reaction. Bioinformatics analysis of the amino acid sequence of NNG lyase identified a PAS (Per-Arnt-Sim) domain. PAS domains can be associated with heme cofactors and function as signal sensors in signaling proteins. This is the first instance of a PAS domain present in a denitration enzyme. The NNG biodegradation pathway should provide the basis for the identification of other enzymes that cleave the NON bond and facilitate the development of enzymes to cleave similar bonds in RDX, nitroguanidine, and other nitramine explosives. IMPORTANCEThe production of antibiotics and other allelopathic chemicals is a major aspect of chemical ecology. The biodegradation of such chemicals can play an important ecological role in mitigating or eliminating the effects of such compounds. N-Nitroglycine (NNG) is produced by the Gram-positive filamentous soil bacterium Streptomyces noursei. This study reports the isolation of a Gram-negative soil bacterium, Variovorax sp. strain JS1663, that is able to use NNG as a sole growth substrate. The proposed degradation pathway occurs via a ␤-elimination reaction that releases nitrite from NNG. The novel NNG lyase requires iron(II) for activity. The identification of a novel enzyme and catabolic pathway provides evidence of a substantial and underappreciated flux of the antibiotic in natural ecosystems. Understanding the NNG biodegradation pathway will help identify other enzymes that cleave the NON bond and facilitate the development of enzymes to cleave similar bonds in synthetic nitramine explosives.

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The explosive-degrading cytochrome P450 XplA: Biochemistry, structural features and prospects for bioremediation

Cited by 55 publications

References 41 publications

Unusual Spectroscopic and Ligand Binding Properties of the Cytochrome P450-Flavodoxin Fusion Enzyme XplA

Unusual Spectroscopic and Ligand Binding Properties of the Cytochrome P450-Flavodoxin Fusion Enzyme XplA

Unusual Cytochrome P450 Enzymes and Reactions

Iron-Dependent Enzyme Catalyzes the Initial Step in Biodegradation of N -Nitroglycine by Variovorax sp. Strain JS1663

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