Reprogramming fungal functions for the design of cell factories
The reprogramming of fungal cellular functions needs detailed data of the metabolic and regulatory networks that are of importance to the process. Various ~omics methods, as. e.g. transcriptomics, proteomics and metabolomics, are applied.
Itaconic acid production in A. niger
Itaconic acid is an important building block for the chemical industry. It is used for the production of plastics. Aspergillus terreus is the natural producer of itaconic acid. The precursor for itaconic acid is citric acid, which is produced in high amounts by Aspergillus niger. The aim of this research is to use metabolic engineering for the construction of A. niger cell factories that produce itaconic acid in high levels and to gain a better understanding of the metabolic mechanisms controlling the accumulation of carboxylic acids in A. niger.
Fumaric acid production in A.niger
Fumaric acid is a naturally occurring four carbon dicarboxylic acid that is used to produce valuable compounds for different application areas as pharmaceutical, food, agricultural, chemical industry. Traditionally fumaric acid has been produced from maleic anhydride, a petroleum derivative. The filamentous fungus Rhizopus delemar formerly known as Rhizopus oryzae is able to accumulate high levels of this organic compound.
In our research we are integrating different –omics approaches to identify relevant proteins for the production of fumaric acid in R. oryzae. The outcome of these analyses is being used to re-design A. niger strains for the production of fumaric acid.
Transport processes in the production of organic acids in filamentous fungi
In this research line we study cellular transport processes of organic acids and the sugars that are metabolized to organic acids. We aim to identify and characterize the transporters that are involved in the ‘journey’ of the carbon source in the metabolic process that lead to the secretion of the organic acid. This will yield us a deeper understanding of the processes involved and potentially tools to to improve the production of these organic acids.
Genome-wide metabolic modelling and data integration of organic acid production in filamentous fungi
Despite the wide use of filamentous fungi for industrial organic acid production, the underlying metabolic processes are not yet well known and understood. Semi-random overexpression or knockouts of genes known or expected to be involved in the relevant pathway can lead to more efficient and hence cost-effective production of the desired organic acid. However, a better understanding of the pathway can lead to more directed approaches in metabolic engineering. Data driven modeling can lead to the desired level of understanding, which in turn can lead to better experimental design and execution, and thus save time usually spent for the trial and error cycle. In the given project, data from organic acid production in filamentous fungi is collected and integrated into genome-scale metabolic models. Compartmentalization and the intracellular pH of the organism studied will be taken into consideration in order to lead to a model able to allow targeted modifications in the pathway of the organic acid of interest.
The discovery and application of lipoxygenases
Many materials are made of petroleum derivatives and one of these is plastic, an widely used daily product. Nowadays mankind is looking for different ways in producing plastics independent of petroleum derivatives. Plastic consists of attached polymers. These molecules can be made with help of an enzyme called lipoxygenase (LOX), which converts polyunsaturated fatty acids (PUFA) to fatty acid peroxides. These peroxides are highly reactive and can be degraded to create building blocks for polymer production. In this way plant material, since they contain PUFAs, can be used to produce plastics.