MECHANISMS OF BIOSYNTHETIC FORMATION OF DEOXY SUGARS

脱氧糖在自然界中无处不在，正式的 通过取代一个或多个羟基从普通糖中提取 含氢的基团。这样的替换通常会导致关键的 所产生的糖的生物作用的改变，以及 使产品的新陈代谢发生根本性变化。这个 核糖核酸到脱氧核糖核苷酸的转换是一个有充分证据的 然而，举例来说，新陈代谢的命运和功能也存在类似的差异 存在于己糖和脱氧己糖之间。特别值得注意的是 3，6-二脱氧己糖存在于革兰氏杆菌脂多糖中。 阴性菌。由于内毒素是革兰氏菌的主要表面抗原- 细胞包膜阴性，革兰氏阴性杆菌的免疫异质性。 阴性物种通常归因于O抗原，其中3，6- 双脱氧-己糖在细胞免疫中起着不可或缺的作用 决心。研究还表明，2，6-和4，6- 双脱氧己糖，普遍存在于抗生素中，在 赋予这些天然产品最佳的生物活性。 尽管脱氧己糖的生物学重要性得到了很好的认识， 人们对这些不寻常的糖的生物合成形成知之甚少。 灵感来自于它们在自然界中存在的独特性和 耐人寻味的免疫效果，我们已经开始了一项 3，6-二脱氧己糖--子囊糖形成的研究 假结核耶尔森氏菌。我们的重点一直放在 C-3脱氧的机理研究似乎是通过 一种自由基机制，从根本上不同于 核糖核苷酸还原酶。作为我们持续努力的继续 研究蛔虫糖的生物合成，这项提议勾勒出我们的未来 计划充分描述这种多步骤生物的过程- 转型。这些实验的结果将被用来解决 下列问题：a)靶材的催化和氧化还原性能 酶，b)催化连续步骤的酶之间的相互作用， 以及c)每种酶转化的反应机理。有了这些 3，6-二脱氧己糖途径的实验进展顺利，我们的努力 将被转移到研究生物合成的机制 在抗生素中发现的脱氧己糖。对分子的理解 这些脱氧糖的生物合成基础不仅会 帮助描述酶是如何影响化学转化的 催化这些转化，但也将提供宝贵的知识 设计方法来控制和/或模拟它们的生产和 生物活动。由于糖类残留物在中国的重要性 测定抗生素的生物活性已经很好了 以及一些糖基转移酶参与了 抗生素的生物合成已显示出某种程度的松弛 底物的特殊性，预计新的洞察力来自于 这些研究也将为两种基因转移实验奠定基础。 以及用于定点突变以生产新型或杂交抗生素。

The deoxy sugars are found ubiquitously in nature and are formally derived from common sugars by the replacement of one or more hydroxyl groups with hydrogens. Such a substitution generally causes a critical alteration of the biological role of the resulting sugar, and also induces a fundamental change in the metabolism of the product. The conversion of ribonucleotide to deoxyribonucleotide is a well documented example, however, a similar disparity of metabolic fate and function exists between hexoses and deoxyhexoses. Particularly notable are the 3,6-dideoxyhexoses found in the lipopolysaccharides (LPS) of gram- negative bacteria. Since LPS is the major surface antigen of the gram- negative cell envelope, the immunological heterogeneity among gram- negative species is often attributed to the O antigen, of which the 3,6- dideoxy-hexoses play an indispensable role in the cell's immunological determination. It has also been shown that the 2,6- and 4,6- dideoxyhexoses, found commonly in antibiotics, play crucial roles in conferring optimal biological activity on these natural products. Although the biological importance of deoxyhexoses is well recognized, little is known about the biosynthetic formation of these unusual sugars. Inspired by the uniqueness of their occurrence in nature and the intriguing properties of their immunological effects, we have begun a study to explore the formation of ascarylose, a 3,6-dideoxyhexoses, in Yersinia pseudotuberculosis. Our emphasis has been placed on the mechanistic studies of the C-3 deoxygenation which seems to proceed via a radical mechanism and is fundamentally distinct from that catalyzed by ribonucleotide reductase. As a continuation of our ongoing efforts to study the biosynthesis of ascarylose, this proposal outlines our future plans to fully characterize the course of this multi-step bio- transformation. The results of these experiments will be used to address the following issues: a) the catalytic and redox properties of the target enzymes, b) the interaction between enzymes catalyzing consecutive steps, and c) the reaction mechanism of each enzymatic conversion. With these experiments well under way for the 3,6-dideoxyhexose pathway, our efforts will then be shifted to study the mechanism of the biosynthesis of deoxyhexoses found in antibiotics. An understanding of the molecular basis of the biosynthetic formation of these deoxy sugars will not only aid in delineating how chemical transformations are affected by enzymes catalyzing these conversions, but will also provide invaluable knowledge for designing approaches to control and/or mimic their production and biological activities. Since the significance of sugar residues in determining the biological activity of the antibiotics has been well established, and some of the glycosyl transferases involved in the biosynthesis of antibiotics have been shown to have somewhat relaxed substrate specificity, it is expected that the new insights gained from these studies will also lay groundwork for both gene transfer experiments and for site-directed mutagenesis to produce novel or hybrid antibiotics.