Biological Chemistry

含碳水化合物的分子在自然界中广泛存在，具有多种生物学作用。它们的化学合成具有挑战性，因此，用于合成含碳水化合物分子的新型酶方法具有立体选择性和区域选择性的优势。该研究将通过改变参与糖苷键的区域选择性和立体选择性合成的糖合酶的底物特异性，推进生产新型含糖分子的方法。它将使用一种新颖的、积极的选择策略，基于细菌细胞死亡来选择具有修饰底物特异性的突变糖合酶。目前迫切需要开发这样的方法，以充分认识酶产生含碳水化合物分子的潜力，并且开发方法来改变酶底物特异性对于偶联合成片段的酶系统的重要性不容低估。拟议的研究将：(a)在进化的新酶功能方面取得根本性发现；(b)发展产生酶键形成的正选择方法的能力，(c)导致新的糖苷酶和糖合酶的表征。资金要求使研究生和PDF在杰克曼博士的监督下进行研究。

Carbohydrate-containing molecules are widespread throughout nature and have a multitude of biological roles. Their chemical synthesis is challenging and, therefore, novel enzymatic methods for the synthesis of carbohydrate-containing molecules offer stereoselective and regioselective advantages. The proposed research will advance methods to produce novel carbohydrate-containing molecules by altering the substrate specificity of glycosynthases involved in the regio- and stereoselective synthesis of glycosidic linkages. It will use a novel, positive selection strategy, based on bacterial cell death to select mutant glycosynthases with modified substrate specificity. There exists a strong need to develop such methods to fully realize the potential of enzymes to produce carbohydrate-containing molecules, and the significance of developing methods to alter enzyme substrate specificity for enzyme systems that couple synthetic fragments cannot be understated. The proposed research will: (a) make fundamental discoveries in evolving novel enzyme function; (b) develop the ability to generate a positive selection method for enzymatic bond formation and (c) result in the characterization of novel glycosidases and glycosynthases. Funds are requested to enable a graduate student and PDF to conduct the research under the supervision of Dr. Jakeman.