Theoretical analyses on enantiospecificity of L-2-haloacid dehalogenase (DehL) from Rhizobium sp. RC1 towards 2-chloropropionic acid Aliyu Adamu a, b, * , Roswanira Abdul Wahab c , Firdausi Aliyu a , Fazira Ilyana Abdul Razak c , Bashir Sajo Mienda d , Mohd Shahir Shamsir a , Fahrul Huyop a, ** a Department of Biosciences, Faculty Science, Universiti Teknologi Malaysia, Johor Bahru, 81310, Johor, Malaysia b Department of Microbiology, Faculty of Science, Kaduna State University, Tafawa Balewa way, Kaduna, PMB 2339, Nigeria c Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, 81310, Johor, Malaysia d Department of Microbiology and Biotechnology, Faculty of Science, Federal University Dutse, Nigeria article info Article history: Received 3 April 2019 Received in revised form 2 July 2019 Accepted 20 July 2019 Available online 21 July 2019 Keywords: Theoretical analyses DehL Rhizobium sp. RC1 Enantiospecificity Dehalogenase abstract Dehalogenases continue to garner interest of the scientific community due to their potential applications in bioremediation of halogen-contaminated environment and in synthesis of various industrially rele- vant products. Example of such enzymes is DehL, an L-2-haloacid dehalogenase (EC 3.8.1.2) from Rhizobium sp. RC1 that catalyses the specific cleavage of halide ion from L-2-halocarboxylic acids to produce the corresponding D-2-hydroxycarboxylic acids. Recently, the catalytic residues of DehL have been identified and its catalytic mechanism has been fully elucidated. However, the enantiospecificity determinants of the enzyme remain unclear. This information alongside a well-defined catalytic mechanism are required for rational engineering of DehL for substrate enantiospecificity. Therefore, using quantum mechanics/molecular mechanics and molecular mechanics Poisson-Boltzmann surface area calculations, the current study theoretically investigated the molecular basis of DehL enantiospe- cificity. The study found that R51L mutation cancelled out the dehalogenation activity of DehL towards it natural substrate, L-2-chloropropionate. The M48R mutation, however introduced a new activity towards D-2-chloropropionate, conveying the possibility of inverting the enantiospecificity of DehL from L-to D- enantiomer with a minimum of two simultaneous mutations. The findings presented here will play important role in the rational design of DehL dehalogenase for improving substrate utility. © 2019 Published by Elsevier Inc. 1. Background The growing use of organohalides in the industrial and agri- cultural sectors has resulted in extensive distribution of appreciable quantities of these biologically hazardous compounds into the environment [1]. While the origin of synthetic organohalides in the environment are mainly from anthropogenic activities, it is equally important to note that organohalides from natural sources also exist abundantly in the biosphere [2,3]. Persistence of these compounds in the environment often leads to serious re- percussions, inter alia, widespread pollution, their possible bio- accumulation in the environment alongside increased health issues [4e6]. These challenges are ascribed to the halogen moiety of organohalides that generally reduces their solubility in water and increases lipophilicity [7 ,8]. This in turn amplifies their bio- accumulation in the food chain, as the recalcitrance of organo- halides tends to sequester in the fatty tissues of higher animals. In this respect, efforts in search of efficacious avenues to neutralise and eliminate from the environment these pollutants, must be stepped up. Interestingly, a number of microorganisms are known to pro- duce dehalogenases capable of catalysing the cleavage of carbon- halogen bond in the halogenated compounds, thereby reversing the effects of the halogen-associated environmental pollution [9e12]. One of such enzymes is the DehL from Rhizobium sp. RC1, an * Corresponding author. Department of Microbiology, Faculty of Science, Kaduna State University, Tafawa Balewa way, Kaduna, PMB 2339, Nigeria. ** Corresponding author. Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, 81310, Johor, Malaysia. E-mail addresses: aliyuadamu@kasu.edu.ng, aliyuadamu60@outlook.com (A. Adamu), fahrul@utm.my (F. Huyop). Contents lists available at ScienceDirect Journal of Molecular Graphics and Modelling journal homepage: www.elsevier.com/locate/JMGM https://doi.org/10.1016/j.jmgm.2019.07.012 1093-3263/© 2019 Published by Elsevier Inc. Journal of Molecular Graphics and Modelling 92 (2019) 131e139