Härle, Johannes, Dr.

The integration of orthogonality is a crucial research strategy in the rational design of biological systems for novel
applications. In order to produce such highly predictable orthogonal systems, we propose to employ cell-free systems of highly engineered composition generated from living cells, which are complex enough to reproduce the major synthetic capabilities of living cells - such as the synthesis of natural and artificial saccharides - but are simplified enough to come close to truly engineerable systems. MazProTec, the title of my postdoctoral research project proposes a two-step-strategy: In a first step, with the help of a RNA-interferase, protein synthesis of a growing bacterial cell will be channeled solely to a limited set of system components. In a second step, the cells will be homogenized and the resulting cell-free extract, already enriched in the required protein components, will be subjected to selective hydrolysis of predefined proteins, which would make the performance of the complex system unpredictable. As a proof-of-concept, “MazProTec” implements a preparative 12-step synthesis from cheap glucose and N-acetyl-glucosamine to a valuable antiviral-precursor, N-acetyl-neuraminic acid. The realization of MazProTec gets financially supported as a Marie Curie - Intra-European Fellowship.

Publications

Härle J., Günther S., Weber M., Lauinger B., Luzhetskyy A., and Bechthold A. Rational design of an aryl-C-glycoside catalyst from a bacterial O-glycosyltransferase. Chem. Biol. 18 (4), 520-530 (2011)

Luzhetska M., Härle J., and Bechthold A. Combinatorial and synthetic biosynthesis in actinomycetes. Fortschr. Chem. Org. Naturst. 93, 211-237 (2010)

Härle J., Lauinger B., Dietmann K., and Bechthold A. „Maßgeschneiderte Biokatalysatoren für eine süßere Chemie“, Biospektrum, 03.10, S. 306-308 (2010)

Härle J., Erb A., Weiss H., and Bechthold A. A bacterial glycosyltransferase gene toolbox: generation and applications. Phytochemistry 70, 1812-1821 (2009)

Härle J., and Bechthold A. Chapter 12. The power of glycosyltransferases to generate bioactive natural compounds. Methods Enzymol. 458, 309-333 (2009)

Dangel V., Härle J., Goerke C., Wolz C., Gust B., Pernodet J.L., and Heide L. Transcriptional regulation of the novobiocin biosynthetic gene cluster. Microbiology 155, 4025-4035 (2009)

Eustaquio A.S., Härle J., Noel J.P., and Moore B.S. S-Adenosyl-L-methionine hydrolase (adenosine-forming), a conserved bacterial and archaeal protein related to SAM-dependent halogenases. ChemBioChem. 9, 2215-2219 (2008)

Selected Stations