Wu Zhigang, Zhao Guohui, Li Tiehai, Qu Jingyao, Guan Wanyi, Wang Jiajia, Ma Cheng, Li Xu, Zhao Wei, Wang Peng G, Li Lei
Department of Chemistry and Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
Glycobiology. 2016 May;26(5):493-500. doi: 10.1093/glycob/cwv169. Epub 2015 Dec 23.
Colitose, also known as 3,6-dideoxy-L-galactose or 3-deoxy-L-fucose, is one of only five naturally occurring 3,6-dideoxyhexoses. Colitose was found in lipopolysaccharide of a number of infectious bacteria, including Escherichia coli O55 & O111 and Vibrio cholera O22 & O139. To date, no colitosyltransferase (ColT) has been characterized, probably due to the inaccessibility of the sugar donor, GDP-colitose. In this study, starting with chemically prepared colitose, 94.6 mg of GDP-colitose was prepared via a facile and efficient one-pot two-enzyme system involving an L-fucokinase/GDP-L-Fuc pyrophosphorylase and an inorganic pyrophosphatase (EcPpA). WbgN, a putative ColT from E. coliO55:H5 was then cloned, overexpressed, purified and biochemically characterized by using GDP-colitose as a sugar donor. Activity assay and structural identification of the synthetic product clearly demonstrated that wbgN encodes an α1,2-ColT. Biophysical study showed that WbgN does not require metal ion, and is highly active at pH 7.5-9.0. In addition, acceptor specificity study indicated that WbgN exclusively recognizes lacto-N-biose (Galβ1,3-GlcNAc). Most interestingly, it was found that WbgN exhibits similar activity toward GDP-l-Fuc (kcat/Km= 9.2 min(-1)mM(-1)) as that toward GDP-colitose (kcat/Km= 12 min(-1)mM(-1)). Finally, taking advantage of this, type 1 H-antigen was successfully synthesized in preparative scale.
可立托糖,也被称为3,6 -二脱氧-L-半乳糖或3-脱氧-L-岩藻糖,是仅有的五种天然存在的3,6 -二脱氧己糖之一。可立托糖存在于多种传染性细菌的脂多糖中,包括大肠杆菌O55和O111以及霍乱弧菌O22和O139。迄今为止,尚未对可立托糖基转移酶(ColT)进行表征,这可能是由于糖供体GDP-可立托糖难以获取。在本研究中,从化学合成的可立托糖开始,通过一个简便高效的一锅双酶系统制备了94.6毫克的GDP-可立托糖,该系统涉及L-岩藻糖激酶/GDP-L-岩藻糖焦磷酸化酶和无机焦磷酸酶(EcPpA)。然后克隆、过表达、纯化了来自大肠杆菌O55:H5的假定ColT WbgN,并以GDP-可立托糖作为糖供体对其进行了生化表征。合成产物的活性测定和结构鉴定清楚地表明,wbgN编码一种α1,2-可立托糖基转移酶。生物物理研究表明,WbgN不需要金属离子,在pH 7.5 - 9.0时具有高活性。此外,受体特异性研究表明,WbgN仅识别乳糖-N-二糖(Galβ1,3-GlcNAc)。最有趣的是,发现WbgN对GDP-L-岩藻糖(kcat/Km = 9.2 min(-1)mM(-1))的活性与对GDP-可立托糖(kcat/Km = 12 min(-1)mM(-1))的活性相似。最后,利用这一点,成功地制备了规模的1型H抗原。