Functional analysis of a novel haloalkane dehalogenase DsvA isolated from thermophilic bacterium Saccharomonospora viridis DSM 43017

Klaudia Šarmírová, Jiří Damborský, Radka Chaloupková

Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Faculty of Science, Masaryk University, Kamenice 5/A13, 625 00 Brno, Czech Republic

 

Microorganisms able to grow in extreme conditions, including high concentration of salts, alkaline pH, low or high temperature and organic solvent medium have been an important source of robust enzymes for various practical applications [1]. Haloalkane dehalogenases (HLDs; EC 3.8.1.5) are predominantly bacterial enzymes that catalyze hydrolytic cleavage of a carbon-halogen bond in a broad range of halogenated aliphatic compounds, producing a corresponding alcohol, a halide anion and a proton [2]. These enzymes can be use in bioremediation, decontamination of warfare agents, synthesis of optically pure compounds, biosensing and cell imaging [3].

A novel member of HLD family, DsvA from Saccharomonospora viridis DSM 43017 isolated from peatbogs of Ireland, has been subjected to detailed biochemical characterization in this study. The enzyme was successfully expressed in Escherichia coli BL21(DE3) cells and purified to homogeneity by metalloaffinity chromatography. Proper folding and thermostability was assessed by circular dichroism spectroscopy. Although DsvA exhibited comparable melting temperature (T= 58 °C) with other HLDs isolated from mesophilic organisms, its kinetic stability determined at 45 and 60 °C was significantly higher than the kinetic stability of other HLDs. Interestingly, DsvA possesses only one, instead of two, halide-stabilizing residues in its active site previously observed in majority of characterized HLDs. Despite unusual composition of catalytic residues, DsvA exhibited clear dehalogenase activity. The highest activity of the enzyme was determined towards
1-bromoheptane, 1-iodohexane and1-bromohexane, whereas no activity was detected in the reaction with bulky and cyclic chlorinated substrates. The temperature and pH optima of DsvA were measured with 1-iodohexane. Maximal activity was detected between 45 and 50 °C and at pH 8.9. Steady state kinetic analyses were performed with 1-iodohexane, 1,2-dibromoethane, 1-iodohexane and
1,3-dibromopropane. The complex kinetic mechanism of the enzyme with 1-iodohexane was determined and revealed substrate inhibition. The kinetics of DsvA with 1,3-dibromopropane followed a simple Michelis-Menten dependence, while the kinetics of the enzyme with 1,2-dibromoethane followed a mechanism involving positive cooperative substrate binding. Crystallization of DsvA for structural analysis is currently in progress.

 

1.       Karan, R.; Capes, M. D.; DasSarma, S. (2012) Function and Biotechnology of Extremophilic Enzymes in Low Water Activity.  Aquat Biosyst. 8: 4.

2.       Damborsky, J., Chaloupkova, R., Pavlova, M., Chovancova, E., Brezovsky, J. (2009) Structure-Function Relationship and Engineering of Haloalkane Dehalogenases. In: Kenneth N. Timmis (Ed.), Handbook of Hydrocarbon and Lipid Microbiology, Springer, Berlin, Heidelberg, 1081-1098.

3.      Koudelakova, T.; Bidmanova, T.; Dvorak, P.; Pavelka, A.; Chaloupkova, R.; Prokop, Z.; Damborsky, J. (2013) Haloalkane Dehalogenases: Biotechnological Applications. Biotechnol J 8: 32-45.