Mukherji Ruchira, Varshney Nishant Kumar, Panigrahi Priyabrata, Suresh C G, Prabhune Asmita
Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India.
Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India.
Enzyme Microb Technol. 2014 Mar 5;56:1-7. doi: 10.1016/j.enzmictec.2013.12.010. Epub 2013 Dec 19.
Use of penicillin acylases for the production of semi-synthetic penicillins is well-known. Escherichia coli penicillin G acylase (EcPGA) has been extensively used for this purpose; however, Kluyvera citrophila penicillin G acylase (KcPGA) is assumed to be a better substitute, owing to its increased resilience to extreme pH conditions and ease of immobilization. In the present article we report a new dimension for the amidase activity of KcPGA by demonstrating its ability to cleave bacterial quorum sensing signal molecules, acyl homoserine lactones (AHL) with acyl chain length of 6-8 with or without oxo-substitution at third carbon position. Initial evidence of AHL degrading capability of KcPGA was obtained using CV026 based bioassay method. Kinetic studies performed at pH 8.0 and 50 °C revealed 3-oxo-C6 HSL to be the best substrate for the enzyme with V(max) and K(m) values of 21.37+0.85 mM/h/mg of protein and 0.1+0.01 mM, respectively. C6 HSL was found to be the second best substrate with V(max) and K(m) value of 10.06+0.27 mM/h/mg of protein and 0.28+0.02 mM, respectively. Molecular modeling and docking studies performed on the active site of the enzyme support these findings by showing the fitting of AHLs perfectly within the hydrophobic pocket of the enzyme active site.
使用青霉素酰化酶生产半合成青霉素是众所周知的。大肠杆菌青霉素G酰化酶(EcPGA)已被广泛用于此目的;然而,由于嗜柠檬酸克雷伯菌青霉素G酰化酶(KcPGA)对极端pH条件的耐受性增强且易于固定化,它被认为是更好的替代品。在本文中,我们通过证明KcPGA能够切割细菌群体感应信号分子——酰基高丝氨酸内酯(AHL)(酰基链长度为6 - 8,在第三个碳位置有无氧代取代),报道了KcPGA酰胺酶活性的一个新方面。使用基于CV026的生物测定方法获得了KcPGA具有AHL降解能力的初步证据。在pH 8.0和50°C下进行的动力学研究表明,3 - 氧代 - C6 HSL是该酶的最佳底物,V(max)和K(m)值分别为21.37 + 0.85 mM/h/mg蛋白质和0.1 + 0.01 mM。发现C6 HSL是第二好的底物,V(max)和K(m)值分别为10.06 + 0.27 mM/h/mg蛋白质和0.28 + 0.02 mM。对该酶活性位点进行的分子建模和对接研究通过显示AHLs完美地契合在酶活性位点的疏水口袋中支持了这些发现。