Analysis of the trehalose metabolism in Actinoplanes sp. SE50/110 with regard to acarbose production and byproduct formation
Actinoplanes spp. are Gram-positive aerobic bacteria producing a variety of pharmaceutically relevant substances. Since 1990 the α-glucosidase-inhibitor acarbose is produced and marketed for the treatment of type-2 diabetes mellitus. Actinoplanes sp. SE50/110 produces different acarviostatins depending on the C-source (Wendler et al. 2014) and various acarbose-like byproducts during fermentation. Wehmeier & Piepersberg described 2004 in particular the byproduct component C (acarviosine-trehalose) which is hard to separate from acarbose during downstream processing. It is therefore worthwhile to study the biosynthesis of trehalose in Actinoplanes sp. SE50/110 and to clarify its role in the production of component C.
Aims of the project
In 2008 Lee et al. postulated three putative trehalose synthetic pathways in Actinoplanes and suggested that one of these proteins, the maltooligosyltrehalose synthase TreY of the treXYZ gene cluster plays a role in the formation of component C. The goal of this Ph.D. project is now to elucidate in Actinoplanes sp. SE50/110 the complete machinery for trehalose biosynthesis. This can be achieved by a mutational analysis of trehalose biosynthesis genes. In addition, the transcriptional regulation of the trehalose biosynthesis genes should be analyzed. Furtheron, the influence of a mutated treXYZ gene cluster on the production of acarbose and the formation of component C shall be analyzed by applying metabolomics techniques.
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