Affiliation:
1. Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, 33615 Bielefeld, Germany
Abstract
The pseudo-tetrasaccharide acarbose, produced by Actinoplanes 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 Actinoplanes sp. SE50/110.
Subject
Virology,Microbiology (medical),Microbiology
Reference43 articles.
1. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045;Sun;Diabetes Res. Clin. Pract.,2022
2. International Diabetes Federation (2023, January 09). IDF Diabetes Atlas, 10th Ed. Available online: https://www.diabetesatlas.org/en/.
3. Acarbose, ein therapeutisch eingesetzter Wirkstoff: Biosynthese und Funktion;Wehmeier;BioSpektrum,2004
4. Acarbose: An update of its therapeutic use in diabetes treatment;Laube;Clin. Drug Investig.,2002
5. The biosynthesis of acarbose and validamycin;Mahmud;Chem. Rec.,2001
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