Synthetic protein scaffolds for flavonoid production in Saccharomyces cerevisiae

Specialised plant metabolites, including flavonoids, have valuable bioactive properties for human health. Traditional production methods are time consuming, create a huge amount of waste and are dependent on external factors. Micro-organisms are therefore a very promising alternative, allowing production of these molecules on an industrial scale. Despite the extensive knowledge on Saccharomyces cerevisiae, many bottlenecks still remain in the construction of an industrial relevant strain. Improper balancing of heterologous pathway genes and loss of intermediates due to side reactions by native enzymes decrease the overall yield and could lead to the accumulation of toxic intermediates. Substrate channelling through the formation of an enzyme complex could help overcome these problems. The different enzymes of the heterologous pathway can be individually balanced leading to an optimised pathway flow. By combining the heterologous pathway at a specific site, local substrate availability can be improved and intermediates are more efficiently channelled through the pathway, thereby reducing the risk of side reactions. We are therefore developing various of these synthetic protein scaffolds in order to gain more insight in how these scaffolds help to increase production of flavonoids, thereby searching for guidelines to apply these technique to other interesting metabolites.

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