Acarbose, the first example of a carbophor?

阿卡波糖，卡波佛的第一个例子？

• 批准号: 12815386
• 负责人: Professor Dr. Erwin Schneider
• 金额: --
• 依托单位: Arbeitsgruppe Physiologie von Mikroorganismen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/12815386?language=en
• 关键词: Acarbose; first; example; carbophor

The ¿¿glucosidase inhibitor acarbose, produced by strains of the genera Actinoplanes and Streptomyces, is a member of an unusual group of bacterial secondary metabolites, all of which inhibit various ¿¿glucosidases. Acarbose is used in the treatment of patients suffering from diabetes type II. Actinoplanes produces acarbose as part of a mixture of compounds called ¿acarbose homologs¿ which, depending on the carbon source, differ in the number of glucose residues at both, the reducing and the non-reducing end. Unlike its function as an inhibitor of ¿¿glucosidases, the benefits of acarbose for the producing organism are still not understood. According to a recent hypothesis acarbose and related compounds might function as so called ¿carbophors¿: Actinoplanes is thought to produce acarbose in order to prevent competitors in its natural habitat from utilizing starch as a carbon and energy source. This is achieved by its function as potent inhibitor of ¿¿glucosidases and of transport systems mediating the uptake of malto-oligosaccharides. Increasing amounts of free unbound acarbose can then be used as acceptor molecules for the uptake of glucose or oligosaccharides which are transferred to acarbose by the action of the acarviosyltransferase, AcbD and/or the ¿¿amylases AcbE/Z. The resulting longer homologs are transported into the cytoplasm where glucose units will then be released and shuttled into metabolism. Acarbose is phosphorylated and re-exported to start a new ¿carbophor cycle¿. The carbophor function has not yet been studied in detail and will be analysed in this application.

该葡糖苷酶抑制剂阿卡波糖由游动放线菌属和链霉菌属的菌株产生，是一组不寻常的细菌次级代谢产物的成员，所有这些次级代谢产物都抑制各种葡糖苷酶。阿卡波糖用于治疗患有II型糖尿病的患者。游动放线菌产生阿卡波糖，作为称为阿卡波糖同系物的化合物混合物的一部分，根据碳源的不同，还原端和非还原端的葡萄糖残基数量不同。与其作为葡萄糖苷酶抑制剂的功能不同，阿卡波糖对生产生物体的益处仍不清楚。根据最近的一个假设，阿卡波糖和相关化合物可能起着所谓的carbophors的作用：Actinoplanes被认为产生阿卡波糖，以防止其自然栖息地的竞争对手利用淀粉作为碳和能源。这是通过其作为葡糖苷酶和介导麦芽低聚糖摄取的转运系统的有效抑制剂的功能实现的。然后，增加量的游离未结合阿卡波糖可用作摄取葡萄糖或寡糖的受体分子，所述葡萄糖或寡糖通过阿卡维糖基转移酶AcbD和/或戊淀粉酶AcbE/Z的作用转移至阿卡波糖。产生的较长的同系物被转运到细胞质中，在那里葡萄糖单位将被释放并穿梭进入代谢。阿卡波糖被磷酸化并重新输出以开始新的卡波伏循环。卡波姆的功能尚未被详细研究，将在本申请中进行分析。