Press releases
International research team secures over €1 million to study newly uncovered Roman cult district
Unlocking the Sacred Landscape of Roman Nida
Several years ago, construction work for a new school in Frankfurt led to a discovery of regional importance: a large Roman sanctuary. This was followed by extensive excavations carried out by Frankfurt’s Monument Office. The findings can now be subjected to comprehensive scientific analysis by an interdisciplinary research team. Funding for this work has been jointly secured by the Archaeological Museum Frankfurt, Goethe University Frankfurt, and the University of Basel.
FRANKFURT. This marks another milestone for Roman-period archaeology in Hesse: The German Research Foundation (DFG) and the Swiss National Science Foundation (SNF) have jointly approved more than €1 million to support the analysis of excavations at the large Roman sanctuary in the ancient city of Nida (Frankfurt-Heddernheim). Over the next three years, the funding will enable researchers to conduct a comprehensive investigation of one of the most significant recent archaeological discoveries in Roman Germania.
Grant application spanning Frankfurt and Basel
Applicants for the project “Exploring the dynamics of a Roman sanctuary – Interdisciplinary studies on spatial organisation and depositions at the central sanctuary in Nida-Heddernheim” include the Archaeological Museum Frankfurt (Dr. Carsten Wenzel); the Institute for Archaeological Sciences at Goethe University Frankfurt (Prof. Anja Klöckner, Classical Archaeology; Prof. Markus Scholz, Archaeology and History of the Roman Provinces; Prof. Astrid Stobbe, Archaeobotany); and the Institute for Integrative Prehistoric and Scientific Archaeology (IPNA) at the University of Basel (Prof. Sabine Deschler-Erb (ⴕ), Dr. Barbara Stopp). Additional cooperation partners include Frankfurt’s City Monument Office [Denkmalamt] and the Roman-Germanic Commission (RGK) of the German Archaeological Institute, also based in Frankfurt. The approved research project was officially presented today at a press conference held at the Archaeological Museum of the City of Frankfurt.
Dr. Ina Hartwig, Frankfurt’s City Commissioner for Culture and Science, commented on the project: “The central cult district of Nida represents an archaeological discovery of almost unparalleled significance in Europe. Its comprehensive scholarly investigation will further establish Frankfurt as a hub of international cutting-edge research. The project demonstrates the strength of our research landscape when museums, universities, non-university research institutions, and heritage conservation work hand in hand to make research visible within the city.”
School construction uncovers Roman cult complex
The cult district of Nida was uncovered during excavations conducted by the Monument Office between 2016 and 2018, and again in 2022, in Frankfurt’s Nordweststadt district. In the course of constructing the new “Römerstadtschule,” an area of more than 4,500 square meters in the center of the Roman city was excavated, revealing a walled complex. The site was almost completely excavated and documented using modern archaeological methods. The findings have been preserved in a coherent state, with only minimal post-Roman disturbance.
Marcus Gwechenberger, Frankfurt’s City Councilor for Planning and Housing, emphasized the discovery’s broader significance: “The newly uncovered cult district of the Roman city of Nida is among the most important archaeological finds in Frankfurt in recent years. The funding now makes it possible to scientifically analyze this exceptional discovery in depth. At the same time, it recognizes the continuous and highly professional work of our municipal heritage office. This project also illustrates how urban development and research go hand in hand in Frankfurt. The fact that the discovery was made during construction of the new Römerstadtschule vividly demonstrates how past and future intersect in our city.”
Archaeological Evidence of Roman Cult Practices
The cult site comprises eleven stone buildings constructed in several phases, as well as around 70 shafts and ten pits used for (ritual) depositions. The building layouts are highly unusual and have no known parallels in the Germanic or Gallic provinces of the Roman Empire. More than 5,000 fragments of painted wall plaster, together with bronze fittings from doors and windows, attest to the elaborate architectural design of the structures.
The shafts and pits yielded numerous ceramic vessels and large quantities of plant and animal remains, including fish and birds. These finds are interpreted as remains of ritual meals and offerings made to the gods. To facilitate detailed analysis, 150 samples were collected for archaeozoological and archaeobotanical study.
The analysis of 254 Roman coins and more than 70 silver and bronze garment clasps (fibulae), some of them fully preserved, is central to reconstructing the ritual and sacrificial practices carried out at the site. Such objects are widely attested as offerings and votive gifts in Roman sanctuaries throughout the empire. By contrast, the evidence pointing to possible human sacrifice at the cult district of Nida is entirely exceptional. Despite the excellent state of preservation and the richness of the material record, conclusions regarding the specific deities worshipped at the site remain limited. Inscriptions and iconographic evidence attest to the veneration of several gods, including Jupiter, the chief Roman deity; Jupiter Dolichenus, particularly revered by soldiers; Mercurius Alatheus, god of trade and commerce; Diana, goddess of nature; Apollo, god of healing; and Epona, the Celtic-Roman goddess of fertility. This constellation suggests that the site functioned as a sanctuary of regional importance in which multiple deities were worshipped side by side.
Based on current evidence, the cult district was established at the beginning of the 2nd century CE. A dedicatory inscription from a soldier to Mercurius Alatheus, dated 9 September 246 CE, confirms that the sanctuary remained in use at least until the mid-3rd century CE.
Interdisciplinary Research Team Enables Comprehensive Study
The approval of this large-scale research project underscores the importance of archaeological research in the Frankfurt region. It also serves as a strong example of the close networking of academic institutions within the Rhine-Main area, both among themselves and in collaboration with international partner institutions.
The funding provides a unique opportunity to investigate this regionally significant complex through an interdisciplinary approach. Focusing on the analysis of interior design and depositional practices, the project aims to reconstruct the ritual activities carried out at the site. In doing so, the cult district of Nida will be embedded within the broader cultural and historical context of the sacred landscapes of the Roman north-western provinces. The project will involve five early-career researchers in doctoral and postdoctoral positions across the participating institutions.
One year after the presentation of the “Frankfurt Silver Inscription”: Research on Nida enters the next phase
In addition to the cult district, other excavations conducted by the Monument Office over the past decades have yielded important insights into the settlement history and topography of Nida. Just over a year after the presentation of the “Frankfurt Silver Inscription” – the oldest known Christian written testimony north of the Alps – the Roman city on Frankfurt soil is once again the focus of public attention. The research team now has the unique opportunity to collaboratively explore Roman religions in Frankfurt and investigate temples, sacrifices, and rituals. The high-quality, exceptionally well-preserved findings underscore the exceptional importance of Nida for Roman-period archaeology in Germany. Founded as a military base in the 70s of the 1st century CE, the settlement developed into the economic and cultural center of the Limes region by the early 2nd century. Characterized by remarkable cultural diversity, Nida remained one of the most important urban centers in Roman Germania until its abandonment around 275/280 CE.
Images and captions can be downloaded at: https://www.uni-frankfurt.de/182413177
Selection of quotes from members of the project “Exploring the dynamics of a Roman sanctuary”
“For many years, the Roman city of Nida has been a focal point of Frankfurt’s archaeological heritage work, yielding exceptional discoveries that continue to advance scholarly understanding. Step by step, these findings are bringing the ancient city into clearer focus and highlighting its remarkable importance within the Roman Empire on the right bank of the Rhine. Meticulous excavation and documentation have now revealed a Roman sacred district in Nida whose scale and character are without parallel anywhere in the empire.”
Dr. Andrea Hampel, Frankfurt’s City Monument Office [Denkmalamt]
“Depositional practices can play a decisive role in shaping both the sacralization and the secularization of spaces. Using Roman Nida as a case study, an international and interdisciplinary research project is examining these processes and underscoring the central importance of religious practices in a major urban center located along the Roman frontier.”
Dr. Kerstin P. Hofmann, Roman-Germanic Commission (RGK) of the German Archaeological Institute
“In many ancient sanctuaries, our knowledge is limited to the ground plans of the cult buildings. At Nida, however, the large number of preserved wall-painting fragments allows us to gain far deeper insight into room heights, spatial organization, and interior design. These findings offer a more nuanced understanding of how the sanctuary functioned as a space – and of the ritual practices that can be inferred from its architecture and decoration.”
Prof. Dr. Anja Klöckner, Goethe University Frankfurt, Classical Archaeology
“In most Roman cities, the urban center was defined by a forum. Nida presents a striking exception. Here, excavations have revealed a multi-phase sanctuary comprising several temples – an arrangement that is highly unusual. The complex likely functioned as the spiritual heart of the settlement and may even have served a wider regional role. Might it have been a pilgrimage center? The evidence points to influences from Gaul, the Mediterranean, and the eastern provinces. Deposits from more than eighty shafts and pits preserve traces of ritual activity, including remains of sacred meals – what might be described as ‘holy refuse.’ Might some of this evidence point to a deliberate abandonment or even desecration of the sanctuary in the third century?”
Prof. Dr. Markus Scholz, Goethe University Frankfurt, Archaeology and History of the Roman Provinces
“Animals and animal products appear to have played a central role in ancient religious practice – whether in ritual meals, acts of communication with the divine, or as offerings. For the first time, this interdisciplinary research project enables a comprehensive and systematic examination of these functions at the Roman site of Nida.”
Dr. des. Benjamin Sichert, IPNA, University of Basel
“Plants and plant-based products played an important role in everyday life, including religious practice, in antiquity. At Roman Nida, archaeobotanical research offers a unique opportunity to examine these functions in a differentiated way, while also gaining insight into patterns of cultivation, importation, and the surrounding environment.”
Prof. Dr. Astrid Stobbe, Goethe University Frankfurt, Archaeobotany Laboratory
“The discovery of Nida’s sacred district came as a remarkable surprise, coinciding with my arrival at the Archaeological Museum in the summer of 2016. As curator for the Roman period, it was an exceptional beginning – and an opportunity to develop a long-term project together with colleagues. With its many distinctive features, the sanctuary not only underscores Nida’s outstanding importance within Roman Germania; its systematic study within the DFG-funded project promises far-reaching new insights into religious life and cult practices in the northern reaches of the Roman Empire.”
Dr. Carsten Wenzel, Archaeological Museum Frankfurt
Further Information:
Prof. Dr. Markus Scholz
Archaeology and History of the Roman Provinces
Goethe University Frankfurt
Institute for Archaeological Sciences, Dept. II
Phone +49 (0)69 798-32265
E-Mail m.scholz@em.uni-frankfurt.de
Holger Kieburg M.A.
PR and Science Communication
Archaeological Museum of the City of Frankfurt
Phone +49 (0)69 212-36747
Mobile +49 (0)151 184 01046
E-Mail: holger.kieburg@stadt-frankfurt.de
Editor: Dr. Anke Sauter, Science Communication, PR & Communications Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel. +49 (0)69 798-13066, sauter@pvw.uni-frankfurt.de
New Method from Goethe University Frankfurt Reveals Demographic Risks in Zoo Mammal Populations
Aging Zoo Animals Threaten Long-Term Species Conservation Goals of Modern Zoos
Many mammal populations in European and North American zoos are aging – a trend that jeopardizes the long-term viability of so-called reserve populations and, with it, a core mission of modern zoos in global species conservation. This is the central finding of a new international study published on Wednesday in the journal PNAS.
FRANKFURT/ZURICH. Images of newborn zoo animals regularly attract public attention – yet the impression of cute baby animals is deceptive. Across many species, births are becoming rarer while populations grow steadily older- a development documented by an international study led by the University of Zurich (Switzerland) in collaboration with Goethe University Frankfurt (Germany), Aarhus University (Denmark), Zoo Zurich (Switzerland) and Copenhagen Zoo (Denmark).
For the study, the researchers analyzed the demographic data from a total of 774 zoo mammal populations (361 in North America, 413 in Europe) covering the period from 1970 to 2023. The analysis draws on the global “Species360" database, used by more than 1,200 institutions worldwide. The database records detailed life-history information for individual animals, including age, sex, ancestry, origin, and reproductive status, enabling a systematic assessment of zoo population structures over several decades.
Distorted Age Pyramids
To evaluate population stability, the team examined age pyramids – a standard demographic tool that illustrates the distribution of age groups within a population. Researchers at Goethe University Frankfurt developed a new method for the automated classification of these population pyramids, allowing demographic patterns to be compared across species and regions with greater precision. This approach translates complex population structures into standardized forms – such as pyramids, diamonds, or columns – each associated with different levels of demographic resilience. Prof. Paul Dierkes of Goethe University Frankfurt, who played a key role in developing the method, explains: “Especially for zoos and species conservation, this new methodological approach and the results based on it open up possibilities for clearly communicating demographic developments and making informed decisions."
But what do the different basic shapes tell us? A classic pyramid shape—with many young and reproductive individuals at the base and progressively fewer older animals—indicates a stable and resilient population. Such populations are better equipped to withstand unexpected shocks, including disease outbreaks. The study shows, however, that an increasing number of zoo populations now display diamond- or column-shaped profiles, characterized by relatively few young animals and a high proportion of older individuals. These structures are considered demographically fragile.
The study also shows that, at the same time, the proportion of actively reproducing females has declined sharply: by 49 percent in North American populations and by 68 percent in European populations. In some cases, populations no longer include any females capable of reproduction. Beyond reducing offspring numbers, this trend can disrupt social structures in many mammal species. Reproduction and rearing young animals are fundamental behavioral components and key elements of species-appropriate husbandry.
Species Conservation Goals at Risk
This development is concerning to the researchers and could threaten the species conservation work of modern zoos. Zoos are internationally recognized partners in global species conservation, particularly through the maintenance of reserve populations of endangered species. In a 2023 position paper, the International Union for Conservation of Nature (IUCN) underscores the importance of zoos, aquariums, and botanical gardens in addressing worldwide biodiversity loss. However, a prerequisite for this role is that the reserve populations kept are stable, capable of reproduction, and viable in the long term. Lead author Prof. Marcus Clauss from the Faculty of Veterinary Medicine at the University of Zurich explains: “This trend must be halted and reversed. Zoos can only fulfill their conservation mandate if they maintain demographically stable and resilient reserve populations. That requires more young animals – and fewer old animals."
Prof. Dierkes adds that the implications extend beyond conservation breeding: “Zoos also play a crucial role in education and research. They reach millions of visitors each year, raise awareness of biodiversity loss, the causes of species extinction, and the importance of nature conservation. Zoos are therefore important places of learning that strengthen understanding and support for species conservation in society. In addition, zoos enable important scientific studies on the behavior, reproduction, and health of endangered species. These findings help to improve husbandry in zoos and make conservation measures in the natural environment more effective. Declining animal numbers and aging populations would therefore not only significantly impair species conservation itself, but also the educational and research work of zoos. Consequently, population management in zoos should be more focused on demographic sustainability. Only if the current trend toward aging populations can be reversed will zoos be able to permanently fulfill their contribution to international species conservation."
Publications:
João Pedro Meireles, Max Hahn-Klimroth, Laurie Bingaman Lackey, Nick van Eeuwijk, Mads F. Bertelsen, Severin Dressen, Paul W. Dierkes, Andrew J. Abraham, and Marcus Clauss. Ageing populations threaten conservation goals of zoos, PNAS (2026), doi.org/10.1073/pnas.2522274123
Max Hahn-Klimroth, João Pedro Meireles, Laurie Bingaman Lackey, Nick van Eeuwijk, Mads F. Bertelsen, Paul W. Dierkes, and Marcus Clauss. 2025, A semi-automatic approach to study population dynamics based on population pyramids, MethodsX (2025), doi.org/10.1016/j.mex.2025.103591
Picture download:
www.uni-frankfurt.de/182265514
Caption: The analysis of Meireles and colleagues shows that reproduction, as shown here in the endangered Grévy's zebra (Equus grevyi), is on the decrease across zoo mammal populations (Tim Benz/Zoo Zürich).
Further Information:
Prof. Dr. Paul W. Dierkes
Didactics and Biological Sciences
Goethe University Frankfurt, Germany
+49 (0)69 798-42273
dierkes@bio.uni-frankfurt.de
www.zoobiology-frankfurt.de
Editor: Dr. Phyllis Mania, Science Editor, PR & Communications Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel: +49 (0) 69 798-13001, mania@uni-frankfurt.de
One of Only a Few Devices Worldwide Enables Imaging of Living Cells
A View into the Innermost Workings of Life: First Scanning Electron Microscope with Nanomanipulator in Hesse Inaugurated at Goethe University
Goethe University Frankfurt (Germany) ceremonially commissioned a state-of-the-art cryo plasma-FIB scanning electron microscope with nanomanipulator worth more than 5 million euros on Thursday. The large-scale instrument, supported by the Dr. Rolf M. Schwiete Foundation, is the first of its kind in Hesse and one of only a few in Germany. It enables precise nanobiopsies of biological samples such as tissue or cell aggregates and is a key technology for the Cluster of Excellence SCALE, where researchers investigate the molecular foundations of cells.
FRANKFURT. With a so-called cryo plasma-FIB (Plasma Focused Ion Beam) scanning electron microscope with nanomanipulator, the Goethe University in Frankfurt (Germany) is expanding its research infrastructure with a powerful instrument. The microscope was inaugurated today at the Buchmann Institute for Molecular Life Sciences on the Riedberg Campus – as the first of its kind in Hesse and one of only a few in all of Germany.
The large-scale instrument works with a focused plasma ion beam, which can be used to prepare tiny sections from biological cells – so-called nanobiopsies with dimensions in the nanometer range. The decisive advantage over conventional ion beam microscopes: the plasma beam works more gently and faster, which is particularly important for sensitive biological samples such as water-containing cells. These ultra-thin sections can then be examined using both scanning electron microscopy and transmission electron microscopy. This makes it possible to visualize protein structures in their natural environment or to trace cellular changes in diseases such as Alzheimer's or cancer at the molecular level.
"This microscope bridges medicine and structural cell biology, opening up completely new possibilities for our research," emphasizes Prof. Achilleas Frangakis, who secured the large-scale instrument worth 5.6 million euros. "We can now visualize biological processes under the microscope that were previously hidden – such as how proteins work together in cells in the still unknown physiological context or even how diseases develop at the nanoscale."
The non-profit Dr. Rolf M. Schwiete Foundation provided substantial funding for the microscope, for which it was honored with a plaque on the device. For the Foundation, supporting high-quality medical research projects is a central concern in order to contribute to improving research conditions and advancing medical knowledge.
Prof. Bernhard Brüne, Vice President for Research at Goethe University, emphasized: "Without this generous funding, this acquisition would not have been possible. The device is indispensable for work in the Cluster of Excellence SCALE – it allows researchers to examine the architecture of cells in previously unattainable detail."
SCALE (Subcellular Architecture of Life) is a joint research project of Goethe University and Johannes Gutenberg University Mainz within the Rhine-Main Universities (RMU) alliance, the Max Planck Institutes for Biophysics and Brain Research, and other partners. Researchers there investigate how cellular structures are built and how errors in this molecular blueprint lead to diseases. The new microscope makes it possible to three-dimensionally image and analyze precisely these defective structures in cancer cells or in neurodegenerative diseases.
Prof. Maike Windbergs, Research Dean at the Department of Biochemistry, Chemistry and Pharmacy, noted that the device makes the Frankfurt location significantly more attractive for international collaborations. Prof. Martin Pos, Dean of Studies at the department, also emphasized that students and doctoral candidates here gain access to a technology that is only available at a few locations worldwide – an important building block for their scientific training and later careers.
Prof. Inga Hänelt, spokesperson for the Cluster of Excellence SCALE, stressed that the microscope will be used by researchers from both RMU partner universities as well as the other partners and allows new insights into the subcellular architecture of life.
Initial images have already deciphered a cellular structure that is crucial for human kidney function. The microscope is now available for a wide range of research projects.
Picture download:
https://www.uni-frankfurt.de/182148333
Caption: Prof. Dr. Achilleas Frangakis presents the scanning electron microscope with nanomanipulator supported by the Dr. Rolf M. Schwiete Foundation (image: Uwe Dettmar/Goethe University).
Further Information:
Prof. Dr. Achilleas Frangakis
Institute for Biophysics
Buchmann Institute for Molecular Life Sciences
Goethe-University Frankfurt, Germany
+49 69 / 798 46462
achilleas.frangakis@biophysik.uni-frankfurt.de
https://frangakis.biophysik.org/
Editor: Dr. Phyllis Mania, Science Editor, PR & Communications Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel: +49 (0) 69 798-13001, mania@physik.uni-frankfurt.de
Research team at Goethe University Frankfurt classifies all human E3 ligases – New opportunities for targeted protein degradation therapies
The “broker” family helps tidy up the cell
Cells must continually adjust their protein composition, which includes protein synthesis as well as degradation. Most regulated protein degradation is executed by the ubiquitin–proteasome system (UPS), in which proteins are tagged with ubiquitin and routed to a protein-shredder called proteasome. The enzyme E3 ligase plays a key role here by acting as a “broker” that mediates the labeling of the proteins to be degraded. A research team at Goethe University Frankfurt has now made the first systematic catalog and relationship map of all human E3 ligases and identified 40 of them as potential key players in emerging drug classes such as PROTACs, which are used, for example, to treat cancer.
FRANKFURT. Maintaining cellular order is a major logistical challenge: Individual mammalian cells contain billions of protein molecules, which must be synthesized, deployed, and removed with precision. In the ubiquitin-proteasome system (UPS), proteins destined for degradation are tagged with chains of several ubiquitin proteins and then degraded by the proteasome. The crucial step is the target selection: E3 ligases are enzymes that act as molecular “broker” by binding specific target proteins and coordinating the transfer of ubiquitin from an E2 enzyme.
As an E3 ligase recognizes only a restricted set of target proteins, cells maintain a large and diverse E3 ligase repertoire. A research team at Goethe University Frankfurt, led by Dr. Ramachandra M. Bhaskara from the Institute of Biochemistry II, has now compiled all members of the “broker family” in a catalog and mapped for the first time how human E3 ligases relate to one another, and what that implies for function, substrate recognition, and drug discovery.
A data-driven map of the “E3 ligome”
To describe the broker family – the so-called “E3 ligome” – the researchers performed AI-supported computational comparisons of E3 ligase features and then validated key functional inferences in cell culture experiments. In this way, the Frankfurt researchers defined 13 major families, as well as subfamilies, which capture more similarities between E3 ligase family members than shared amino acid sequences and structural characteristics. Bhaskara explains: “Our data-driven machine-learning approach reveals family-specific functions. For example, members of one family are important for DNA repair programs and for preventing unplanned cell death, while those of another are involved in antiviral defense.”
Beyond their role in protein degradation, E3 ligases are also implicated in ubiquitin signaling, which is not used for protein degradation, broadening their relevance across cellular pathways and disease mechanisms.
Implications for next-generation therapeutics
The new E3 ligase map is particularly relevant for targeted protein degradation strategies used in novel types of active pharmaceutical substances such as PROTACs. PROTACs (Proteolysis Targeting Chimeras) are bifunctional molecules that bring an E3 ligase into proximity with a disease-relevant protein, triggering ubiquitin tagging and proteasomal destruction of the disease-relevant protein. Although the field has advanced rapidly, most existing PROTAC programs rely on only a small number of well-characterized E3 ligases.
By systematically analyzing the full E3 ligome, the team identified 40 additional E3 ligases that may be suitable for PROTAC development—and, importantly, the family relationships may help researchers repurpose or adapt ligands and design principles across related E3 ligases. This could widen the range of tissues, cellular contexts, and diseases that targeted degradation can reach.
Open resource for the research community
Because many groups worldwide are developing targeted degradation approaches, the Goethe University team has made the complete E3 ligome publicly available via a dedicated database, enabling other researchers to build on the classification and functional insights.
Publication: Arghya Dutta, Alberto Cristiani, Siddhanta V. Nikte, Jonathan Eisert, Yves Matthess, Borna Markusic, Cosmin Tudose, Chiara Becht, Varun Jayeshkumar Shah, Thorsten Mosler, Koraljka Husnjak, Ivan Dikic, Manuel Kaulich, Ramachandra M. Bhaskara: Multi-scale classification decodes the complexity of the human E3 ligome. Nature Communications (2025) https://doi.org/10.1038/s41467-025-67450-9
Picture download:
https://www.uni-frankfurt.de/181983680
Captions:
1.Sun of families: Researchers at Goethe University have elucidated the relationships among all 462 catalytic human E3 ligases; E3 ligases also support non-degradative functions. Image: Ramachandra M. Bhaskara, Goethe University Frankfurt
2. PROTACs and E3 ligases: PROTACs link a target protein (protein of interest, POI) with an E3 ligase, which mediates the ubiquitin labeling (yellow) of the POI via an E2 enzyme. The POI is then degraded in the proteasome shredder (blue). Image: Institute of Biochemistry II, Goethe University Frankfurt
Contact:
Dr. Ramachandra M. Bhaskara
Team Leader Computational Cell Biology
Institute of Biochemistry II
Goethe University Frankfurt, Germany
Tel. +49 (0)69 7984-2526
Bhaskara@med.uni-frankfurt.de
https://biochem2.com/people/bhaskara-ramachandra-m
Editor: Dr. Markus Bernards, Science Editor, PR & Communications Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel: +49 (0) 69 798-12498, bernards@em.uni-frankfurt.de
Protein Engineering Enables Sustainable Production of Industrially Important Fatty Acids
From Palm Oil to Designer Enzymes: Frankfurt Researchers Reprogram Yeast Cells
Fatty acids derived from palm oil and coconut oil are found in countless everyday products, but their extraction drives deforestation. Researchers at Goethe University Frankfurt (Germany) have now reprogrammed the enzyme fatty acid synthase to produce custom fatty acids of any chain length. With just two targeted modifications, the enzyme can be redirected from producing the usual 16-carbon fatty acids to generating shorter chains. In collaboration with a partner laboratory in China, the engineered fatty acid synthase was implemented in yeast strains to enable sustainable bioreactor-based production of industrially relevant fatty acids.
FRANKFURT. Whether laundry detergents, mascara, or Christmas chocolate – many everyday products contain fatty acids from palm oil or coconut oil. However, the extraction of these raw materials is associated with massive environmental issues: rainforests are cleared, habitats for endangered species are destroyed, and traditional farmers lose their livelihoods. The team led by Prof. Martin Grininger at Goethe University in Frankfurt, Germany, has now developed a biotechnological approach that could enable a more environmentally friendly production method.
A Molecular Assembly Line with Precise Control
At the heart of this research is an enzyme called fatty acid synthase (FAS) – a type of molecular assembly line that builds fatty acids in all living organisms. “FAS is one of the most important enzymes in a cell's metabolism and has been fine-tuned by evolution over millions of years," explains Grininger.
The enzyme typically produces palmitic acid, a 16-carbon fatty acid that serves as a building block for cell membranes and energy storage. Industry, however, primarily requires shorter variants with 6 to 14 carbon atoms, which today are sourced from plant oils produced on large-scale oil palm plantations linked to deforestation and biodiversity loss. The decisive advantage of the new, FAS-based method: “Fundamentally, our advantage lies in the very precise control of chain length. We can theoretically make any chain length, and we're demonstrating this with the example of C12 fatty acid, which otherwise can only be obtained from palm kernels or coconut," says Grininger.
Understanding Through Modification
Grininger and his team have significantly contributed to understanding the molecular foundations of FAS over the past 20 years. They discovered that chain length is regulated by the interplay between two subunits: ketosynthase repeatedly elongates the chain by two carbon atoms while thioesterase cleaves off the finished chain as a fatty acid. “We then asked ourselves whether we could go beyond analysis and build FAS with new chain length regulation," says Grininger. “True understanding begins when you can change or customize a phenomenon."
Two Targeted Interventions Lead to Success
Grininger's doctoral student Damian Ludig took up this idea. “We asked what would happen if we specifically intervened in the interaction between these two subunits," Ludig explains. “Could we then control the chain length of the fatty acids that are produced?"
Ludig employed protein engineering methods where individual amino acids can be exchanged or entire protein regions modified. “Two changes to FAS through protein engineering ultimately led us to our goal," says Ludig. “In the ketosynthase subunit, I first exchanged one amino acid which resulted in chains being extended only with low efficiency beyond a certain length. Additionally, I replaced the thioesterase subunit with a similar protein from bacteria that shows activity in cleaving short chains." Depending on further adjustments, Ludig was able to produce short- and medium-length fatty acids.
From Frankfurt to Dalian
Collaboration with Prof. Yongjin Zhou's research group at Dalian Institute of Chemical Physics, Chinese Academy of Sciences, ultimately achieved breakthrough results. Supported by the German Research Foundation (DFG) and the National Natural Science Foundation of China (NSFC), Zhou and his lab succeeded in developing yeast strains that produce fatty acids containing only 12 carbon atoms instead of 16. Various designer FAS from Grininger's lab were integrated into these yeasts for optimization.
Both laboratories have already filed patents for their technologies. “On the Chinese side, Unilever was involved in this project. Our development has thus far taken place without industrial participation. However, we are striving for a collaboration with an industry partner in order to bring the technology into application," says Grininger.
Thinking Ahead: From Fatty Acids to Pharmaceuticals
In a second project, Felix Lehmann from Grininger's lab took the research even further by investigating how universally applicable FAS are for tailored biosyntheses: “This question is also driven by necessity – to continually develop chemical processes towards more sustainable green chemistry," explains Grininger.
The specific question was: Can FAS be redirected to make not only fatty acids, but also entirely different compounds, such as styrylpyrones? These molecules are precursors to substances derived from kava plants that attract medical interest due to their potential anxiolytic properties. Here, too, Lehmann achieved success with relatively few modifications: “First we cut away part of FAS that we didn't need for our target products; then we altered ketosynthase so that cinnamic acid could be used as starting material," he explains. The team even integrated another protein into the FAS structure so it became part of multi-enzyme complex.
“In this project we systematically examined how entire biosynthetic pathways can be constructed with FAS from readily available building blocks," Grininger explains. While the results do not yet have immediate practical applications, they provide important guidance for the future design of novel synthases.
At the Intersection of Chemistry and Biology
“Our lab has made significant strides towards biocatalysis and biotechnological applications over recent years, driven by the contributions of many projects and collaborations. We will continue down this path", Grininger summarizes. “Within the Cluster of Excellence SCALE, we will also use this enzyme to generate tailored biomembranes, whose analysis will help deepen our understanding of key organelles such as the endoplasmic reticulum and mitochondria."
Whether technology can indeed alleviate palm oil issues now depends on successful scaling up alongside industry partners. The scientific foundation has certainly been laid and the lab still has many ideas to explore.
Publications:
Damian L. Ludig, Xiaoxin Zhai, Alexander Rittner, Christian Gusenda, Maximilian Heinz, Svenja Berlage, Ning Gao, Adrian J. Jervis, Yongjin J. Zhou & Martin Grininger. Engineering metazoan fatty acid synthase to control chain length applied in yeast. Nature Chemical Biology (2026) https://doi.org/10.1038/s41589-025-02105-w
Felix Lehmann, Nadja Joachim, Carolin Parthun, Martin Grininger. Design of a Multienzyme Derived from Mouse Fatty Acid Synthase for the Compartmentalized Production of 2-Pyrone Polyketides. Angewandte Chemie International Edition (2025). https://doi.org/10.1002/anie.202511726
Picture download:
https://www.uni-frankfurt.de/181986496
Caption:
File “Palmoil_Shutterstock": Palm oil plantations often stretch for kilometers and pose a problem for humans and animals alike (Image: Shutterstock).
File “Biosynthesis_LehmannGrininger_EN": Schematic representation of biosynthesis in a cell (top) and in the laboratory (bottom). The designer enzyme shortens the chain length of the fatty acid (Image: Felix Lehmann & Martin Grininger/Goethe University).
Further Information:
Prof. Dr. Martin Grininger
Institute for Organic Chemistry and Chemical Biology
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt
Max-von-Laue-Str. 15
60438 Frankfurt am Main, Germany
+49 (0)69 798 42705
grininger@chemie.uni-frankfurt.de
https://www.greeninger-chemistry.com/
Editor: Dr. Phyllis Mania, Science Editor, PR & Communications Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel: +49 (0) 69 798-13001, mania@physik.uni-frankfurt.de
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