Henri Ingelman defended his doctoral thesis “Systems-level characterisation and improvement of of Clostridium autoethanogenum metabolism”

Henri Ingelman defended his doctoral thesis “Systems-level characterisation and improvement of of Clostridium autoethanogenum metabolism” on the 26th of September, 2024. Thesis supervisors are Professor Kaspar Valgepea and Dr. Lorena Azevedo de Lima. Congratulations!

Acetogenic bacteria have become attractive biocatalysts for their ability to convert greenhouse gases into valuable products through gas fermentation. This technology has the potential to mitigate climate change and waste management problems, but challenges remain for global deployment. Firstly, our understanding of acetogen metabolism is limited and genotype-phenotype links are not clearly resolved. In addition, genetic engineering is in its relative infancy compared to model organisms and is hampered by the fact that the functions of most genes are currently unclear. 

This thesis focused on overcoming these challenges by combining gas fermentation with systems biology, adaptive laboratory evolution (ALE), and genetic engineering. The aim was to investigate specific growth rate-dependent metabolism and to use ALE to obtain C. autoethanogenum strains with improved characteristics. The thesis also aimed to improve the understanding of genotype-phenotype links. 

The work presents quantitative data on specific growth rate-dependent acetogen metabolism and the gas fermentation process. Results show that accelerated growth of C. autoethanogenum increases the productivity of industrially relevant compounds and advances our understanding of transcriptional regulation in acetogens. In addition, the thesis concludes that ALE can be used to engineer strains that grow faster, grow on minimal medium, and are robust in autotrophic continuous cultures. In addition, effects of three mutations from ALE were investigated in-depth by construction of three wild-type based strains and characterisation in bottle and bioreactor cultures. The findings show that ALE-inspired genetic engineering can yield C. autoethanogenum strains with notably improved traits. In addition, convergent evolution was detected and several novel targets for genetic engineering to acquire improved microbial cell factories were identified.

Read the thesis here