Nölting Sophia, März Camilla, Jacob Lucas, Persicke Marcus, Schneiker-Bekel Susanne, Kalinowski Jörn
Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, 33615 Bielefeld, Germany.
Microorganisms. 2023 Mar 27;11(4):848. doi: 10.3390/microorganisms11040848.
The pseudo-tetrasaccharide acarbose, produced by sp. SE50/110, is a α-glucosidase inhibitor used for treatment of type 2 diabetes patients. In industrial production of acarbose, by-products play a relevant role that complicates the purification of the product and reduce yields. Here, we report that the acarbose 4-α-glucanotransferase AcbQ modifies acarbose and the phosphorylated version acarbose 7-phosphate. Elongated acarviosyl metabolites (α-acarviosyl-(1,4)-maltooligosaccharides) with one to four additional glucose molecules were identified performing in vitro assays with acarbose or acarbose 7-phosphate and short α-1,4-glucans (maltose, maltotriose and maltotetraose). High functional similarities to the 4-α-glucanotransferase MalQ, which is essential in the maltodextrin pathway, are revealed. However, maltotriose is a preferred donor and acarbose and acarbose 7-phosphate, respectively, serve as specific acceptors for AcbQ. This study displays the specific intracellular assembly of longer acarviosyl metabolites catalyzed by AcbQ, indicating that AcbQ is directly involved in the formation of acarbose by-products of sp. SE50/110.
由sp. SE50/110产生的假四糖阿卡波糖是一种用于治疗2型糖尿病患者的α-葡萄糖苷酶抑制剂。在阿卡波糖的工业生产中,副产物起着重要作用,使产品纯化变得复杂并降低了产量。在此,我们报道阿卡波糖4-α-葡聚糖转移酶AcbQ可修饰阿卡波糖及其磷酸化形式阿卡波糖7-磷酸。通过用阿卡波糖或阿卡波糖7-磷酸与短α-1,4-葡聚糖(麦芽糖、麦芽三糖和麦芽四糖)进行体外测定,鉴定出具有一至四个额外葡萄糖分子的延长的阿维菌素代谢物(α-阿维菌素-(1,4)-麦芽寡糖)。揭示了与麦芽糖糊精途径中必不可少的4-α-葡聚糖转移酶MalQ具有高度功能相似性。然而,麦芽三糖是优选的供体,阿卡波糖和阿卡波糖7-磷酸分别作为AcbQ的特异性受体。本研究展示了由AcbQ催化的更长的阿维菌素代谢物的特定细胞内组装,表明AcbQ直接参与了sp. SE50/110阿卡波糖副产物的形成。