Andrei Ogonkov

As part of my doctoral studies in biology at Leipzig University, I spent a six-month research stay at ETH Zurich. I joined the working group of Professor Dr Jörn Piel (Department of Bacterial Natural Products). The Department had thirty staff members from around the world with diverse research backgrounds. We had a very pleasant working atmosphere, and I experienced strong support from the team for my work. My research colleagues were highly ambitious, independent and autonomous but in a very team-oriented manner. I was able to establish a large number of personal and professional contacts during my time in Zurich.

The Covid-19 situation stabilised around the time I arrived in Zurich. Our working group was at long last able to go on a group trip to Fräkmüntegg and everybody was excited, after the long period of isolation. It was my first mountain hike, and I really wanted to see more of Switzerland after this wonderful experience. I was out and about a lot at the weekends and the first thing I wanted to see was Zurich’s sights. As a biologist, I had to see the botanical gardens and the zoo, of course. I particularly enjoyed the Masoala rainforest hall at the zoo. I spent some quiet days walking by Lake Zurich. In Switzerland you are always surrounded by beautiful nature.

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Impressions of the Swiss landscape

I was introduced to many new methods and approaches during my research stay. The implementation of 3D models for proteins, for example, helped me to gain a better understanding of the enzyme structure. Exchange of specialist knowledge and practical skills is extremely important in research, and I am very happy that my research stay at ETH Zurich enabled me to broaden my horizon.

During my stay, we examined an unusual polyketide synthase (PKS) PksA from the Arctic cyanobacterium Chlorogloea sp. CCALA 695. The genome of Chlorogloea sp. CCALA 695 features four genes that are believed to be responsible for producing type I PKS. PKS are generally involved in the secondary metabolism of many organisms, despite their similarities to fatty acid synthases with regard to the identity and structural organisation of enzymatic domains. The natural substances produced by PKS exhibit a wide range of biological activities and they have cytotoxic, antimicrobial or cholesterol-lowering effects, for example. The polyketide that is produced by PksA and its biological function are unknown. The goal of this project is therefore a functional characterisation of PksA including structural clarification of the polyketide. Based on the predicted domain organisation, the architecture of PksA resembles iterative type I PKS that can be found in fungi. Termination is most likely facilitated by the C-terminal aminoacyltransferase (AaTr) domain. However, the polygenetic analysis between fungi and (cyano) bacterial AaTr domains suggests that this PKS evolved largely independently.

There has been speculation that the AaTr domain catalyses a decarboxylating condensation reaction between the acyl carrier protein (ACP) bound polyketid and a specific amino acid, which is required for release, as can be observed in biosynthesis of certain mycotoxins. The AaTr domain of PksA was produced through heterologous expression in E. coli. In vitro reactions with the purified AaTr domain enabled us to identify the specific amino acids that are required for termination. In addition, we obtained provisional evidence of a so-called Schiff base. Our results showed strong similarity between the AaTr domain and serine palmitoyl transferases that are involved in biosynthesis of sphingolipids. These new findings should enable us to optimise the in vitro experiments for the entire PksA enzyme, in order to characterise the iterative type I PKS and its product from the cyanobacterium.

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Lake Zurich in the evening

I could not have realised my stay at ETH Zurich without funding from the DAAD. I would like to thank Heike Schreitz in particular, for her competent and swift help with any formal matters. Special thanks go to the selection committee and Stefanie Lohmann for granting me the Professor Bingel Scholarship. My sincere thanks is also owed to Professor Piel and his team, and I would like to say thank you to my supervisors Dr Amy Fraley and Dr Clara Chepkirui for enriching my stay both professionally and personally.

ETH Zurich has a very good reputation and offers top-quality education, making the institution ideal for my research project. My time at ETH contributed to my doctoral project successfully, and I am very confident that the generated data can lead to a publication. (Editor's note: Meanwhile, the article is freely accessible as an open access publication). The final outcome of my stay at ETH was highly satisfactory, despite the Covid-19 situation, and I would recommend this experience to everyone.