Metabolic channeling plays an important role in the biosynthesis of numerous natural products. It has inspired researchers to mimic this approach by bringing enzymes together in an artificial way. Different approaches have been employed, such as non-specific co-immobilization, and the construction of gene fusions. Recently, new site-specific strategies have been developed to modify proteins in a controlled manner. Surprisingly, this kind of approach has not been used yet for the controlled, direct linkage of different enzymes. We were therefore motivated to use site-specific modification strategies for the creation of an artificial metabolon. As a model system, the synthesis and glycosylation of resveratrol was chosen. The application of multiple conjugation reactions and the use of heterotelechelic linkers enabled us to connect the enzymes in a well-defined manner. This strategy guaranteed that heteromeric complexes were formed, in which enzymes with a sequential role in the metabolic route were coupled to each other.

Synthetic metabolons for piceid production via bioconjugation

244th National Meeting (2012)

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