Carbon source dependent biosynthesis of acarviose metabolites in Actinoplanes sp. SE50/110.

Abstract

In this work the biosynthesis of the type 2 diabetes mellitus therapeutic acarviosyl-maltose (acarbose) and related acarviose metabolites produced by Actinoplanes sp. SE50/110 was studied in liquid minimal medium supplemented with the defined carbon sources maltose, glucose, galactose or mixtures of maltose/glucose and maltose/galactose. Quantifying acarviosyl-maltose by HPLC and UV detection revealed that only cultures grown in maltose-containing minimal media produced acarviosyl-maltose in significant amounts. A qualitative analysis of the cytosolic and extracellular proteome for the presence of proteins from the acarbose biosynthesis gene cluster showed that these were not only synthesized in maltose-containing media, but also in media with glucose or galactose as the sole carbon source. A LC-MS-based detection method was applied to test the hypothesis that different acarviose metabolites are produced in media with maltose, glucose or galactose. The analysis revealed that a spectrum of acarviose metabolites (acarviose with 1-4 glucose equivalent units) was formed under all tested conditions. As expected, in maltose-containing minimal media acarviosyl-maltose was produced as the major component exceeding the remaining minor components by 2-3 orders of magnitude. In minimal medium supplemented with glucose acarviosyl-glucose was the major component, while in minimal medium with galactose no major component was present. Based on the results presented, a model for the intracellular biosynthesis of major and minor acarviose metabolites was developed.

• Authors: Sergej Wendler, Vera Ortseifen, Marcus Persicke, Andreas Klein, Armin Neshat, Karsten Niehaus, Susanne Schneiker-Bekel, Frederik Walter, Udo F Wehmeier, Jörn Kalinowski, Alfred Pühler
• Journal: Journal of biotechnology (J Biotechnol) Vol. 191 Pg. 113-20 (Dec 10 2014) ISSN: 1873-4863 [Electronic] Netherlands
• PMID: 25169663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Bacterial Proteins
• Maltose
• Carbon
• Glycosyltransferases
• ACBD protein, Actinoplanes sp. 50-110
• Glucose
• Acarbose
• Galactose

Topics

• Acarbose (chemistry, metabolism, therapeutic use)
• Bacterial Proteins (chemistry, metabolism)
• Carbon (chemistry)
• Diabetes Mellitus, Type 2 (drug therapy)
• Galactose (chemistry)
• Glucose (chemistry)
• Glycosyltransferases (chemistry, metabolism)
• Humans
• Maltose (chemistry)