Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution

2016-12-01
Kalyoncu, Sibel
Heaner, David P.
Kurt, Zöhre
Bethel, Casey M.
Ukachukwu, Chiamaka U.
Chakravarthy, Srinivas
Spain, Jim C.
Lieberman, Raquel L.
Nitroaromatic compounds are typically toxic and resistant to degradation. Bradyrhizobium species strain JS329 metabolizes 5-nitroanthranilic acid (5NAA), which is a molecule secreted by Streptomyces scabies, the plant pathogen responsible for potato scab. The first biodegradation enzyme is 5NAA-aminohydrolase (5NAA-A), a metalloprotease family member that converts 5NAA to 5-nitrosalicylic acid. We characterized 5NAA-A biochemically and obtained snapshots of its mechanism. 5NAA-A, an octamer that can use several divalent transition metals for catalysis in vitro, employs a nucleophilic aromatic substitution mechanism. Unexpectedly, the metal in 5NAA-A is labile but is readily loaded in the presence of substrate. 5NAA-A is specific for 5NAA and cannot hydrolyze other tested derivatives, which are likewise poor inhibitors. The 5NAA-A structure and mechanism expand our understanding of the chemical ecology of an agriculturally important plant and pathogen, and will inform bioremediation and biocatalytic approaches to mitigate the environmental and ecological impact of nitroanilines and other challenging substrates.
NATURE CHEMICAL BIOLOGY

Suggestions

Fate and degradation kinetics of nonylphenol compounds in aerobic batch digesters
Omeroglu, Seçil; Sanin, Faika Dilek (2014-11-01)
Nonylphenol (NP) compounds are toxic and persistent chemicals that are not fully degraded either in natural or engineered systems. Current knowledge indicates that these compounds concentrate in sewage sludge. Therefore, investigating the degradation patterns and types of metabolites formed during sludge treatment are important for land application of sewage sludge. Unfortunately, the information on the fate of nonylphenol compounds in sludge treatment is very limited. This study aims to investigate the bio...
Enantioselective michael addition of 1-nitropropane to nitroolefins with 2-aminodmap and quinine based bifunctional organocatalysts
Kanberoğlu, Esra; Tanyeli, Cihangir; Department of Chemistry (2015)
1,3-dinitro compounds are key materials in the synthesis of a variety of important fine chemicals. Moreover, they are reduced to 1,3-diamines which are starting materials of biologically active compounds, agrochemicals and pharmaceuticals. In this study, ((2S,3S)-1,3-dinitropentan-2-yl)benzene was synthesized via the Michael addition of 1-nitropropane to trans-β-nitrostyrene in the presence of chiral bifunctional 2-aminoDMAP and quinine based organocatalysts. In the first part of study, reaction conditions ...
Attenuation of polychlorinated biphenyls (PCBs) under anaerobic conditions
Kaya, Devrim; Sanin, Faika Dilek; İmamoğlu, İpek; Department of Environmental Engineering (2012)
Polychlorinated biphenyls (PCBs) are toxic and persistent anthropogenic contaminants. Concern on their adverse health effects has led to their regulation in air, water and/or soil in addition to sludge. Hence, removal of PCBs in various matrices, including transformer oils (TO) is a priority. This study aims to investigate PCB-118 and Aroclor 1254 toxicity and dechlorination by varying certain critical experimental components including electron donor (sludge or fatty acids), inocula (unacclimated or acclima...
Uptake of Divalent Ions (Mn+2 and Ca+2) by Heat-Set Whey Protein Gels
Öztop, Halil Mecit; MCCARTHY, Michael J.; ROSENBERG, Moshe (2012-02-01)
Divalent salts are used commonly for gelation of polymer molecules. Calcium, Ca+2, is one of the most common divalent ions that is used in whey protein gels. Manganese, Mn+2, is also divalent, but paramagnetic, enhancing relaxation decay rates in magnetic resonance imaging (MRI) and can be used as a probe to understand the behavior of Ca+2 in whey protein gels. The objective of this study was to investigate the diffusion of Ca+2 and Mn+2 ions in heat-set whey protein gels by using MRI and nuclear magnetic r...
Asymmetric organocatalytic sulfa-michael reactions of thioglycolate with isatin derived nitroalkenes
Sağesen, Selin; Tanyeli, Cihangir; Department of Chemistry (2018)
Organosulfur compounds are present in many natural products and drugs. Sulfa-Michael reaction is the prominent method to synthesize these molecules. The novel bifuctional organocatalysts developed in our research group enable sulfa-Michael reaction to ocur asymmetrically. In this thesis, biologically active isatin derived nitroalkenes were chosen as Sulfa-Michael acceptors. Addition of methyl thioglycolate to isatin derived nitroalkenes in the presence of the bifunctional organocatalysts was studied under d...
Citation Formats
S. Kalyoncu et al., “Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution,” NATURE CHEMICAL BIOLOGY, pp. 1031–1039, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/42673.