Towards hybrid metabolism in living cells:integrating transition-metal catalysis in biosynthetic pathways

Bacteria such as E. coli can be engineered to make them produce useful pharmaceuticals or non-natural molecules, for example building blocks for plastics which are otherwise obtained from crude oil. These molecules, however, can be toxic to the bacteria itself, limiting the productivity of the bacteria and economic benefit. If the obtained molecule can be converted further into a less toxic or more valuable product, usefulness of the developed process can be increased. Performing this conversion with transition-metal catalysis would be interesting as compounds may be obtained which nature cannot produce on its own. In order to enable the combination of transition-metal catalysis and bacteria, a way to make them compatible has to be found.In this thesis, two different ways of achieving this compatibility, though catalyst selectivity or compartimentalization, are described in separate occasions and when combined. Using catalyst selectivity or compartimentalization together, two transition-metal catalyzed reactions were performed in the presence of E. coli bacteria, converting the molecule produced by bacteria into a derivative. This shows that catalyst selectivity and compartmentalization are key factors in enabling the combination of transition-metal catalysis and bacteria. It also demonstrates that the combination of transition-metal catalysis with bacteria can open up new synthesis routes from which new molecules can be obtained and which offer a possibility to use renewable resources which are obtained from bacteria in low yields