Beteiligung der Evolution von sekundärmetabolischen Aminotransferasen an der Entstehung der Biodiversität von Aminoglycosid Antibiotika.

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2-Deoxystreptamine-containing aminoglycosides (2DOS-AGA) are potent antibiotics with diverse chemical structures. We have recently sequenced 12 production gene clusters of their main representatives. The evolution of two aminotransferase families is involved in their biodiversity: (1)bifunctional L-glutamine: ketocyclitol aminotransferases ( S -enzymes; class IV ATs) and (2) aminoglycoside 6¿-aminotransferases ( B -enzymes; class III ATs). Both gene families encoding these aminotransferases have undergone various evolutionary diversifications, such as gene duplication and subsequent acquirement of new substrate ranges or mutational drift to alterations in second substrate recognition patterns in the genes for bifunctional ATs. We attempt to analyse their comparative enzymology and protein 3-D structure for an elucidation of the differences in substrate range. The hypothesis that acceptance of two diverse substrates by the bifunctional enzymes is based on existence of two separate binding sites delivering to the same active center in S enzymes will be tested. - Collaborations will mainly involve enzymology of secondary sugar modification and glycosyltransfer (Bechthold group, Freiburg) and 3-D structure elucidation of aminotransferases (Stubbs group, Halle).