Analysis of the transcriptional regulation of the acarbose biosynthesis gene cluster of Actinoplanes sp. SE50/110
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, using improved derivatives of the wild-type strain Actinoplanes sp. SE50/110 (ATCC 31042). The deciphered genome sequence of Actinoplanes sp. SE50/110 wildtype strain (Schwientek et al. 2012) was the basis for developing the full branch of 'omics'-technologies for Actinoplanes, such as transcriptomics (Schwientek at al. 2014), proteomics (Wendler et al. 2013, 2015) and metabolomics (Wendler et al. 2014). With this information it is now possible to conduct experiments which provide insights into the transcriptional regulation networks of Actinoplanes sp. SE50/110.
Aims of the project
The Ph.D. project proposed aims to analyze the transcriptional regulation of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110. At first a genome-wide survey of the transcriptional regulatory repertoire in Actinoplanes sp. shall be established. At second protein binding studies with selected promotor sequences of acarbose biosynthesis genes should be performed to identify putative transcriptional regulators. Finally knock-out mutants of putative transcriptional regulators of the acarbose biosynthesis should be constructed. These mutants can be used to identify the corresponding regulatory gene networks. The knowledge on the transcriptional regulation of the acarbose biosynthesis gene cluster should then be used to optimize acarbose production.
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