Beteiligung der Evolution von sekundärmetabolischen Aminotransferasen an der Entstehung der Biodiversität von Aminoglycosid Antibiotika.

次级代谢转氨酶的进化参与氨基糖苷类抗生素生物多样性的出现。

• 批准号: 5453166
• 负责人: Professor Dr. Wolfgang Piepersberg
• 金额: --
• 依托单位: Arbeitsgruppe Chemische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5453166?language=en
• 关键词: Beteiligung; der; Evolution; von; sekund

2-Deoxystreptamine-containing aminoglycosides (2DOS-AGA) are potent antibiotics with diverse chemical structures. We have recently sequenced 12 production gene clusters of their main representatives. The evolution of two aminotransferase families is involved in their biodiversity: (1)bifunctional L-glutamine: ketocyclitol aminotransferases ( S -enzymes; class IV ATs) and (2) aminoglycoside 6¿-aminotransferases ( B -enzymes; class III ATs). Both gene families encoding these aminotransferases have undergone various evolutionary diversifications, such as gene duplication and subsequent acquirement of new substrate ranges or mutational drift to alterations in second substrate recognition patterns in the genes for bifunctional ATs. We attempt to analyse their comparative enzymology and protein 3-D structure for an elucidation of the differences in substrate range. The hypothesis that acceptance of two diverse substrates by the bifunctional enzymes is based on existence of two separate binding sites delivering to the same active center in S enzymes will be tested. - Collaborations will mainly involve enzymology of secondary sugar modification and glycosyltransfer (Bechthold group, Freiburg) and 3-D structure elucidation of aminotransferases (Stubbs group, Halle).

含2-脱氧链胺氨基糖苷（2DOS-AGA）是一种化学结构多样的强效抗生素。我们最近对其主要代表的12个生产基因簇进行了测序。两个转氨酶家族的进化涉及其生物多样性：(1)双功能l -谷氨酰胺：酮环醇转氨酶（S -酶；IV类ATs）和(2)氨基糖苷6¿-转氨酶（B -酶；III类ATs）。编码这些转氨酶的两个基因家族都经历了不同的进化多样化，例如基因复制和随后获得新的底物范围，或者突变漂移到双功能ATs基因中第二底物识别模式的改变。我们试图分析它们的比较酶学和蛋白质三维结构，以阐明底物范围的差异。双功能酶接受两种不同底物的假设是基于S酶中存在两个独立的结合位点，这些结合位点传递到相同的活性中心，这一假设将被验证。-合作将主要涉及二次糖修饰和糖基转移的酶学（Bechthold group, Freiburg）和转氨酶的三维结构解析（Stubbs group, Halle）。