Dissertation defence (Biochemistry): MSc Magdalena Joanna Niemczura
MSc Magdalena Joanna Niemczura defends the dissertation in Biochemistry titled “Synthetic biology approach for polyketide engineering and enzyme function elucidation” at the University of Turku on 15 August 2025 at 12.00 (University of Turku, Agora, XXII Auditorium, Turku).
Opponent: Professor Ville Santala (Tampere University)
Custos: Professor Mikko Metsä-Ketelä (University of Turku)
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Summary of the Doctoral Dissertation:
Actinobacteria are soil-dwelling, Gram-positive bacteria that produce compounds with antibiotic and anticancer properties. The discovery of those compounds revolutionised medicine, providing powerful tools for battling diseases that plagued humanity for millennia. Nowadays, the alarming rise in antibiotic resistance and a constantly growing number of cancer cases worldwide demand innovative solutions. To address these challenges, we turned to synthetic biology, a field that applies discoveries of genetic engineering to redesign and reprogram biosynthetic pathways. We used a technique called BioBricks, which allows us to build biological circuits from standardised parts. The modularity of this approach enables mixing and matching the parts to achieve the most optimised yield.
We built deoxysugar pathways and introduced them in plasmids into a non-native Streptomyces host. The host was already carrying a construct which allowed for the expression of a non-glycosylated intermediate, 8-demethyl-tetracenomycin C. As a result, the bacteria produced eight glycosylated compounds, four of which were not described before. This demonstrates how synthetic biology can help expand the diversity of secondary metabolite derivatives, potentially leading to the creation of new active compounds with reduced side-effects and accelerate the development of new drugs.
Secondly, we investigated the function of key enzymes in the chartreusin pathway. Chartreusin is a secondary metabolite with anticancer properties, but limited bioavailability. Fully understanding its biosynthetic pathway opens the door to creating new chartreusin derivatives with improved bioavailability. We identified a three-enzyme cascade responsible for the double dehydration of auramycinone into resomycin C and described three enzymes responsible for it – ChaU, ChaX and ChaJ.
These findings highlight the importance of synthetic biology in new compound discovery.
Opponent: Professor Ville Santala (Tampere University)
Custos: Professor Mikko Metsä-Ketelä (University of Turku)
***
Summary of the Doctoral Dissertation:
Actinobacteria are soil-dwelling, Gram-positive bacteria that produce compounds with antibiotic and anticancer properties. The discovery of those compounds revolutionised medicine, providing powerful tools for battling diseases that plagued humanity for millennia. Nowadays, the alarming rise in antibiotic resistance and a constantly growing number of cancer cases worldwide demand innovative solutions. To address these challenges, we turned to synthetic biology, a field that applies discoveries of genetic engineering to redesign and reprogram biosynthetic pathways. We used a technique called BioBricks, which allows us to build biological circuits from standardised parts. The modularity of this approach enables mixing and matching the parts to achieve the most optimised yield.
We built deoxysugar pathways and introduced them in plasmids into a non-native Streptomyces host. The host was already carrying a construct which allowed for the expression of a non-glycosylated intermediate, 8-demethyl-tetracenomycin C. As a result, the bacteria produced eight glycosylated compounds, four of which were not described before. This demonstrates how synthetic biology can help expand the diversity of secondary metabolite derivatives, potentially leading to the creation of new active compounds with reduced side-effects and accelerate the development of new drugs.
Secondly, we investigated the function of key enzymes in the chartreusin pathway. Chartreusin is a secondary metabolite with anticancer properties, but limited bioavailability. Fully understanding its biosynthetic pathway opens the door to creating new chartreusin derivatives with improved bioavailability. We identified a three-enzyme cascade responsible for the double dehydration of auramycinone into resomycin C and described three enzymes responsible for it – ChaU, ChaX and ChaJ.
These findings highlight the importance of synthetic biology in new compound discovery.
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