New Core Facility "Natural Product Isolation and NMR" at MPI-TM

Interview with the Core Facility Leaders Anna Wacker and Karsten Siems

The new Core Facility for Natural Product Isolation and NMR at the Max Planck Institute for Terrestrial Microbiology is led by Dr. Anna Wacker and Dr. Karsten Siems. It focuses on isolating pure compounds from microorganisms and their high-resolution structural characterization. This is essential for researching biological activity and the targeted optimization of future active substances. The Core Facility aims to accelerate and enhance the efficiency of natural product research.
 

What makes a natural product a potential lifesaver? The answer lies in its molecular architecture. The precise three-dimensional structure of a molecule determines its biological activity—for example, by binding to receptors like a key fits a lock. Without this knowledge, targeted optimization and understanding disease mechanisms are not possible. This is the focus of the new Core Facility "Natural Product Isolation and NMR" at the Max Planck Institute for Terrestrial Microbiology.

"To understand the function of natural products from microorganisms, it is necessary to know their exact structure and to have these substances available to investigate their biological activity. Until now, isolation has been the most time-consuming step, but this will change with the new Core Facility at our institute," says MPI Director Prof Dr Helge Bode.

Under co-direction of Dr Anna Wacker and Dr Karsten Siems, the Core Facility combines the extraction of pure substances from microorganisms with high-resolution structural characterisation. In this interview, Anna and Karsten talk about how they combine isolation and NMR, what motivates them, and why their work is important for developing tomorrow's pharmaceuticals.

You are the new co-leaders of the Core Facility 'Natural Product Isolation and NMR'. What does the Core Facility do?

Karsten: We isolate and clarify structures. I am primarily responsible for isolation. We extract pure substances from microorganisms (e.g. from 5-litre fermentations). Often, you start with 5–10 g of extract and end up with 1–2 mg of pure substance. This is then analytically characterised – we record all the data. The chemical structure can be derived from this data and the production history. Often, you can predict it, but sometimes there are surprises. You need the pure substance in order to research its effects (e.g. as an active ingredient).

Does that mean that sometimes you know what you are looking for and sometimes you do not?

Karsten: Yes. Often, we know because the organisms are genetically engineered, with biosynthesis genes identified or specifically modified. I spent the last 30 years working for a company that worked exclusively with wild-type organisms. In those cases, the products were unknown in advance.

The Core Facility focuses on two aspects: isolation and NMR. Are these to be viewed separately from each other?

Anna: We work closely together, but our specializations differ slightly. Karsten also performs NMR, while I have limited involvement in isolation. I am specifically responsible for maintaining the NMR equipment. These spectrometers analyze structures ranging from small molecules to proteins, DNA, and RNA.

How would you describe NMR? Is it like a 'photo' of the structure?

Anna: No, that's more what X-ray crystallography or cryo-EM does. NMR is an indirect method: it measures electromagnetic signals from atomic nuclei, from which the relationships between atoms are inferred. The result is a characteristic "fingerprint" spectrum. Structural analysis requires extensive manual interpretation, as no fully automated solution exists. Discrepancies indicate errors, similar to solving Sudoku puzzles. Ambiguities are resolved using complementary methods, such as mass spectrometry or specialized NMR experiments.

Why is the exact structure so important?

Anna: First, it is essential for patent protection; more importantly, it is necessary to understand the mechanism of action. Active compounds exert biological activity through structural interactions with cellular partners, such as receptors. To modify active compounds or understand their mechanisms, we need to know the three-dimensional structure, especially at critical binding sites. This is the only way to identify which structural elements are essential for the desired effect. Modifications at incorrect sites cause the compound to no longer fit the target molecule, resulting in loss of activity. This information is crucial for optimizing activity and clarifying mechanisms.

Is the Core Facility also available to other groups?

Anna: Yes, to the institute and its cooperation partners. We are well equipped and aim to utilize our capacities efficiently, similar to the utilization of MRI machines. Consolidating resources under one roof facilitates logistics and enables the development of on-site expertise. We seek to optimize and automate processes to increase throughput and relieve researchers of routine tasks. This accelerates research, allowing colleagues specializing in molecular biology, for example, to work more efficiently.

Tell us a little about your background: Karsten, you come from industry?

Karsten: Yes, I studied and completed my PhD in Berlin, after which I worked for Analyticon from 1993 until the end of 2025. We isolated substances from plants, fungi and bacteria, and performed synthesis and analysis for the pharmaceutical, cosmetics and food industries, using methods similar to those used here.

And how about you, Anna?

Anna: I studied in Frankfurt and earned my doctorate there. After parental leave, I worked part-time in my doctoral group, coordinating research and administrative tasks. My doctoral thesis focused on NMR, and later I supervised projects on RNA structure. During the pandemic, I contributed significantly to elucidating SARS-CoV-2 RNA structures.

What interests you most about your new job?

Karsten: I wanted to return to fundamental research and I am fascinated by natural substances and structures. At the company, that became less of a focus.

Anna: Among other things, I am looking forward to getting colleagues with a background in molecular biology excited about NMR, including young scientists.

How do you balance your work life?

Karsten: I am interested in nature. I study birds and I am interested in orchard meadows.

Anna: I don't strictly separate work and life — I simply love my job. But I balance it out with volleyball (I play in regional competitions), spending time with my family, and working in our garden.

This is the first time you've worked together. How do you organise your joint leadership?

Anna: It just comes naturally from our areas of focus, but we work closely together. They're supposed to be intertwined. We won't divide it up so strictly. We're training each other. Science is always teamwork.

Dear Anna and Karsten, thank you for the interview!