2 July 2024

Congratulations William!

PhD defence

On 19 June DynaMo PhD scholar William Thomas Wajn defended his PhD thesis and was awarded the PhD degree with a great performance.

In front of colleagues, family and friends, William Thomas Wajn successfully defended his PhD thesis entitled ‘Engineering Saccharomyces cerevisiae for glucosinolate biosynthesis'.

William after the PhD defence with the traditional PhD hat.

Summary:

Plants synthesize a vast array of diverse specialized metabolites, which have served as nutraceuticals, pharmaceuticals, and essential components in various industries for centuries. However, the native production of these compounds in plants occurs in minute quantities through tightly regulated and complex pathways. Extracting these valuable compounds from biomass demands significant resources, including land, water, and time investments. To overcome these challenges, microbial biosynthesis of plant specialized metabolites has emerged as a promising research area, aiming to enable scalable, on-demand production with minimal land and water usage. Glucosinolates, a class of amino acid-derived plant defence compounds characteristic of the Brassicales order, have garnered attention as potential nutraceuticals due to their health-promoting effects.

In his thesis, William has focused on producing glucosinolates using yeast (Saccharomyces cerevisiae) as heterologous host. He established the core structure pathway capable of converting homophenylalanine into the corresponding glucosinolate, 2-phenylethyl glucosinolate. He identified a major bottleneck caused by insufficient supply of the co-factor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and optimized it to the highest reported titer of any glucosinolate in microorganisms. Additionally, he used (together with dr. Michal Poborsky) Escherichia coli strains expressing the chain elongation machinery (that does not functionally express in yeast) to establish the longest pathway reported co-cultivation of E. coli and S. cerevisiae. Through optimization of media components and screening ratios, he successfully synthesized and optimized the de novo production of 2-phenylethyl glucosinolate.

Principal supervisors:

Professor Barbara Ann Halkier, Section for Molecular Plant Biology
Facility Manager, Christoph Crocoll, Section for Molecular Plant Biology

Assessment committee:

Professor Sotirios Kampranis, (Chair)

Professor Irina Borodina, DTU Biosustain. Novo Nordisk Center for Biosustainability (External member)

PhD Morten Nørholm. Head of Department, Microbial Expression Engineering, Novo Nordisk (External member)

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