Structure Elucidation and Biosynthesis of Microbial Polypeptides with New Posttranslational Modifications

Microcins and lantibiotics are two rapidly growing families of polypeptide antibiotics. Both are synthesized ribosomally as precursor proteins, which undergo posttranslational modifications of the amino acids serine, threonine and cysteine. These modifications result in the formation of sulfide rings, 2,3-didehydroamino acids, D-amino acids, oxazole and thiazole rings. Posttranslationally modified polypeptides are limited in their conformational space. Therefore a number of 3D structures were determined by multidimensional NMR. In cooperation with the Department of Microbiology, the biosynthesis is being investigated and new modifying enzymes are being characterized with respect to their structure and specificity. For the first time, the construction of new modified peptides proved to be possible by protein engineering. These techniques also provide the molecular tools for the development of a new anti-acne drug as well as new gyrase inhibitors.

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