TU Delft’s IMB section is an international research group that currently harbours 20 PhD students, 5 postdocs and 10 different nationalities. Its infrastructure for controlled cultivation of micro-organisms includes 46 bioreactor set-ups, while its molecular facilities include MiSeq and MinION sequencing equipment, an Affymetrix microarray set-up and a fluorescence-activated cell sorter. Analysis of genome sequence data is done in close collaboration with the Delft Bioinformatics group. Recent highlights from IMB’s metabolic engineering research include the development of bakers’ yeast strains for production of bioethanol from pentose sugars (now commercialized by DSM), the functional expression of a pyruvate-dehydrogenase complex in the yeast cytosol and the successful implementation in yeast of Calvin-cycle enzymes, thereby strongly reducing formation of glycerol as a byproduct of anaerobic yeast cultures. IMB actively collaborates with international academic groups and with major fermentation industries, including DSM, Amyris and Heineken.
Jean-Marc Daran and Jack Pronk, who will jointly supervise the PAcMEN PhD students at the Delft University of Technology, are principal investigators in the TU Delft’s Industrial Microbiology section (IMB). Both are driven by a wish to understand, improve and extend applications of micro-organisms in industrial processes. Saccharomyces yeasts serve as their main experimental systems. Jean-Marc specializes in microbial genetics and genomics, with an emphasis on unravelling and (re)constructing complex, industrially microbial genotypes.
Jack’s specialization is in microbial physiology, in which he tries to quantify, understand and improve microbial performance by cultivation and analysis of wild-type and engineered micro-organisms under controlled conditions. In their joint research, Jean-Marc and Jack like to integrate targeted metabolic engineering strategies with non-targeted approaches such as laboratory evolution and random mutagenesis. They continuously seek to implement novel, cutting-edge techniques in synthetic biology, genomics and analysis in their research.
Project 11: Engineering vitamin synthesis in S. cerevisiae
Project 12: Cofactors engineering in yeasts
Saccharomyces cerevisiae is already a key cell factory for production of biofuels, bulk and fine chemicals from renewable carbohydrate feedstocks. Attractive properties of this yeast include robust performance in large-scale industrial processes and, especially after the recent implementation of in-vivo assembly techniques and CRISPR-Cas9, an amazing accessibility to genetic modification. In recent years, many compounds have been produced with engineered S. cerevisiae strains. The two PAcMEN PhD projects at TU Delft will focus on improving the yeast chassis by enabling simpler, cheaper production processes and by extending the range of product pathways that can be functionally expressed. To this end, the projects will focus on an important limitation of S. cerevisiae: its inability to synthesize several vitamins and cofactors that are necessary for yeast growth and/or for functional expression of heterologous product pathways. The two PhD students will focus on solving these problems by expressing heterologous pathways towards these compounds, using a combination of synthetic biology, laboratory evolution and sequence-based reverse engineering of laboratory-evolved strains.