Researchers from Goethe University and TU Munich decode biosynthesis of aryl polyene pigments
FRANKFURT. Bacteria can protect themselves from the attack of free radicals using specific natural products in their membranes. The biosynthesis of one of the most common protective pigments that could also be of interest for the medical and cosmetic industries has now been uncovered by researchers from Goethe University and TU Munich.
Aryl polyene are yellow pigments produced by bacteria living in widely varying environments such as soil, the human intestines or other ecological niches. Embedded in the membrane of the bacteria, they serve as protection against oxidative stress or reactive oxygen species. The latter can damage the cells once it enters the bacterial cell.
Although it was previously known which proteins were responsible for the formation of aryl polyenes, it was unclear how they produced the yellow pigments. The research group Molecular Biotechnology led by Professor Helge Bode (Goethe University Frankfurt), working in collaboration with the research group led by Assistant Professor Nina Morgner (Faculty of Chemistry at Goethe University) and Professor Michael Groll (Technical University of Munich), was able to reconstitute the biosynthesis of aryl polyenes in the test tube and thus elucidate the function of individual biosynthesis steps.
“Aryl polyenes' anti-oxidative properties are similar to those of carotenoids, but are produced completely differently," says Gina Grammbitter, who investigated this system as part of her doctoral work. “Its biosynthesis is very similar to the formation of fatty acids, but also exhibits unexpected differences," adds Nina Morgner. “Together with Michael Groll's group, we were able to identify unusual complexes of the proteins involved and determine their structure."
As the researchers demonstrate in the current issue of the Journal of the American Chemical Society, aryl polyenes are produced via a novel biosynthesis pathway and are presumably located directly in the membrane of the bacteria. However, aryl polyenes are only part of a much larger natural product: “What's still missing is the formation and structure of this overall structure," explains Gina Grammbitter, who is currently working on exactly this issue.
Research in this field continues. The next step is to investigate the interaction of the individual enzymes and the role of aryl polyenes, e.g. in the microbiome of humans. Because of their anti-oxidation properties, aryl polyenes may also be of interest to the cosmetic industry.
Publication: Grammbitter GLC, Schmalhofer M, Karimi K, Schöner TA, Tobias NJ, Morgner N, Groll M, Bode HB. An Uncommon Type II PKS Catalyzes Biosynthesis of Aryl Polyene Pigments. J Am Chem Soc. 2019 Mar 25. doi: 10.1021/jacs.8b10776.
An image may be downloaded here: http://uni-frankfurt.de/77157898
Caption: Biosynthesis of the yellow aryl polyene protective pigments from simple precursors that are very widespread in bacteria.
Further Information: Professor Helge B. Bode, Molecular Biotechnology, Faculty of Biological Sciences, Riedberg Campus, Tel.: +49 69 798-29557, H.Bode@bio.uni-frankfurt.de.
Cooperation between Applied Computational Linguistics lab of Goethe University and Springer Nature
FRANKFURT. Springer Nature published its first machine-generated book, compiled using an algorithm developed by researchers from Goethe University. This collaboration broke new ground with the first machine-generated book to be published by a scholarly publisher.
The book offers an overview of new research publications on lithium-ion batteries – a structured, automatically generated summary of a large number of current research articles. It gives researchers an overview of the latest research in this rapidly growing field, allowing them to manage the information efficiently. The book is available as free download.
The process, developed under the direction of Assistant Professor Christian Chiarcos with the Applied Computational Linguistics (ACoLi) lab of Goethe University, consists of various components that analyse text content so that relevant publications from the content platform SpringerLink are automatically selected and processed. These peer-reviewed Springer Nature publications undergo a similarity-based clustering in order to arrange the source documents into coherent chapters and sections.
Succinct summaries of the articles are created within the chapters. Extracted and paraphrased passages from the source documents are referenced by hyperlinks which allow readers to further explore the original document. Automatically created introductions, tables of contents and reference sections facilitate the orientation within the book.
“This publication has allowed us to demonstrate the degree to which the challenges of machine-generated publications can be solved when experts from scientific publishers collaborate with computer linguists," explained Professor Chiarcos. “The project also enabled us to better understand the expectations of authors, editors, publishers and consumers – with regard to both scientific and economic requirements."
Henning Schoenenberger, Director Product Data & Metadata Management at Springer Nature, added: “While research articles and books written by researchers and authors will continue to play a crucial role in scientific publishing, we foresee many different content types in academic publishing in the future: from yet entirely human-created content creation to a variety of blended man-machine text generation to entirely machine-generated text. This prototype is a first important milestone we reached, and it will hopefully also initiate a public debate on the opportunities, implications, challenges and potential risks of machine-generated content in scholarly publishing."
Publication link: https://link.springer.com/book/10.1007/978-3-030-16800-1
Further information: Assistant Professor Dr Christian Chiarcos, Applied Computer Linguistics, Faculty of Computer Science and Mathematics, Bockenheim Campus, Phone: +49 69 798 22463:, email@example.com, http://acoli.cs.uni-frankfurt.de/
Albumin in high doses improves cardiac function and reduces inflammation
FRANKFURT. Decompensated cirrhosis is a chronic disease linked to numerous complications in its final stage. Professor Jonel Trebicka from Goethe University was involved in carrying out a pilot study demonstrating that the long-term administration of albumin in high doses stabilizes the circulatory function of these patients and protects them from sepsis.
“I was spending a research period at the clinic in Barcelona at the time the clinical study Pilot-PRECIOSA was underway and discussed the results in patients with severe sepsis with the researchers on site," says Professor Jonel Trebicka, hepatologist at the Medical Clinic I at Goethe University.
Albumin is a protein that occurs in human blood where it fulfils numerous tasks. Cirrhosis of the liver reduces its levels, so that patients with decompensated cirrhosis, the stage at which serious complications occur, have been treated with albumin before, but only for short periods.
In the Pilot-PRECIOSA study involving 22 European partners, two groups of patients with decompensated cirrhosis were treated with albumin for three months. One group received a low dose, the other a high dose. Patients who received the higher dose exhibited improved cardiac function and a reduction in the concentration of inflammation markers in their blood.
This treatment is being tested on a larger group of patients in the current follow-up study PRECIOSA, in which Professor Trebicka and Assistant Professor Tanya Welzel from the Medical Clinic I are involved.
“This result is enormously important for our work in the recently founded Micro-Predict Consortium, in which we investigate the importance of the intestinal microbiome in liver diseases: now we will look for microbiome markers that signal a responsiveness to albumin, so that we can apply the therapy more precisely in the future."
In the MICROB-PREDICT project, specialised doctors work together with leading experts in microbiome and medical technology, and the patient organisations ELPA and the Home of Hepatology (EASL). The supporting organization is the European Foundation for the Study of Chronic Liver Failure (EFCLIF), which also sponsored the Pilot-PRECIOSA study. EFCLIF is a foundation connecting a network of more than 100 university hospitals across Europe within EASL, including the University Hospital at Goethe University.
Publication: Fernandez J et al.: Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patient with Decompensated Cirrhosis, in: Gastroenterology (2019), doi: https://doi.org/10.1053/j.gastro.2019.03.021
An image may be downloaded at: http://www.uni-frankfurt.de/77108559
Caption: The Project Microb-Predict directed by Professor Jonel Trebicka will look for albumin markers in intestinal microbiome for a more precise albumin treatment for decompensated cirrhose in the future.
Further information: Professor Jonel Trebicka, Medical Clinic I, Faculty of Medicine, Niederrad Campus, Telefon: +49 178 531 8838, firstname.lastname@example.org
Goethe University secures three ERC Advanced Grants / A total of € 7.7 million for five years
FRANKFURT. Three ERC Advanced Investigator Grants from the European Research Council, amounting to € 7.7 million in total, will go to researchers at Goethe University in Frankfurt. The sociologist Professor Markus Gangl examines whether economic inequality poses a threat to liberal society. The economist Professor Bernd Skiere researches the economic dimensions of cookies, and Helge Bode, Professor for Molecular Biotechnology, aims to discover new drugs based on natural products.
“For the first time, Goethe University has succeed in securing three ERC projects simultaneously in one round of applications. It's a very special challenge for us, and I am delighted," commented University President Professor Birgitte Wolff regarding the announcement of the award winners. “The development of synthetic drugs from natural substances, researching economic mechanisms in the Internet and the scientific examination of the connection between social inequality and societal stability – with their projects, our scientists are investigating important issues of our day," says Wolff.
SYNPEP" Project reprograms natural peptides as drugs
Many clinically used drugs are peptides, which are often produced by microorganisms such as bacteria or fungi. They include important antibiotics such as vancomycin, daptomycin and penicillin, immune suppressors such as cyclosporine, and anti-cancer drugs such as bleomycin. To alter these peptides, the enzymes producing them have to be reprogrammed. This also allows the production of non-natural peptides which do not occur in nature and which might have beneficial or superior properties compared to the original peptide. This is the goal of SYNPEP (Synthetic biology of non-ribosomal peptide synthetases to generate new peptides), headed by Helge B. Bode, Professor for Molecular Biotechnology at the Faculty of Biological Sciences at Goethe University. The project will be funded for five years with € 3.16 million.
Helge Bode came to Goethe University in 2008 when he was appointed Merck Endowed Chair for Molecular Biotechnology. He works on all aspects of microbial natural products, with particular focus on the natural function of these molecules. His group studied this within the framework of an ERC Starting Grant from 2013 through 2018. His second emphasis is on the manipulation of non-ribosomal peptide synthetases, which are the focus of the ERC Advanced Grant just awarded.
“POLAR" Project focuses on social inequality
Professor Markus Gangl was awarded an Advanced Grant for the research project POLAR (Polarization and its discontents: does rising economic inequality undermine the foundations of liberal societies?). The project is dedicated to the issue of whether increasing economic inequality contributes to the undermining of important pillars of Western-liberal society. Professor Gangl and his project team will use survey data from approximately 30 countries in an empirical study of the relationship between growing inequality and social mobility, social cohesion, and the acceptance of democratic values and institutions. The project will be funded with approximately € 2.5 million.
Markus Gangl has been at Goethe University since 2011 as a Professor of Sociology in the area of social stratification and social policy; he also is an Honorary Fellow at the Department of Sociology of the University of Wisconsin-Madison, USA. Before joining Goethe University he held professorships at the University of Wisconsin-Madison and at the University of Mannheim. Professor Gangl is an elected member of the Lepoldina (German National Academy of Sciences), an elected member of the Board of the Research Committee 28 (Social stratification and mobility) of the International Sociological Association, and the Editor-in-Chief of the European Sociological Review, the most important European journal in his field. He currently directs the CORRODE project, also funded by the European Research Council (ERC), which empirically investigates the socio-economic consequences of the financial crisis.
“COOKIES" project researches the value of cookies for advertisers
Cookies allow companies to collect information about users in the Internet. This information is often used to improve the performance of online advertising, which website publishers rely on in order to finance the “free" content to which their users have become accustomed. Yet, the collection of information leads to a loss of privacy. Accordingly, EU policy makers have put forward initiatives to restrict cookie usage (e.g., General Data Protection Regulation (GDPR), upcoming ePrivacy Regulation).
So far, there exists very little empirical knowledge on the trade-off between user privacy and the economic value that website publishers, advertisers, and even users derive from cookies. As a result, policy makers have no way of telling whether their restrictions on cookies have the intended positive consequences for user privacy, or whether any benefits are outweighed by negative effects on the profits of companies—which policy makers also seek to nurture. The research project COOKIES (Economic Consequences of Restrictions on the Usage of Cookies) by Professor Bernd Skiera aims to close this gap. In the project, several data sets will be analysed, including a cookie dataset containing prices for online advertisements from more than 2.8 billion (anonymous) cookies, and an implementation dataset that shows how thousands of websites implemented the EU General Data Protection Regulation that went into effect in 2018. The funding for this project amounts to almost € 2 million.
Bernd Skiera has been Chair for Electronic Commerce at Goethe University since 1999. In Handelsblatt's 2014 ranking, he was named the highest performing research professor in business economics in Germany, Austria and Switzerland. Thirteen of his former doctoral students are now professors in Germany, Austria, the USA, England and Spain; nine are in tenured positions.
Pictures may be downloaded here: http://www.uni-frankfurt.de/77056325
Further information: Prof. Dr. Helge B. Bode, Institute for Molecular Biosciences, Faculty of Biological Sciences, Riedberg Campus, Tel. +49 69 789-29557, H.Bode@bio.uni-frankfurt.de; Prof. Dr. Markus Gangl. Institute for Sociology, Faculty of Social Sciences, Westend Campus, Tel. + 49 69 798-36633, E-Mail email@example.com; Prof. Dr. Bernd Skiera, Chair for Electronic Commerce, Faculty of Business and Econimics, Westend Campus, Tel. +49 69 798-34649, E-Mail firstname.lastname@example.org; Homepage: https://www.marketing.uni-frankfurt.de/professoren/skiera/prof-dr-bernd-skiera.html.
Researchers decode mechanism for diversifying bioactive phenazines
FRANKFURT. Bacteria produce a cocktail of various bioactive natural products in order to survive in hostile environments with competing (micro)organisms. In the current issue of Nature Chemical Biology, researchers at Goethe University demonstrate that they do so by modifying basic structures, similar to the approach taken in pharmaceutical research.
Phenazines are widespread and chemically diverse bacterial natural products that can fulfil various biological functions. Like antibiotics, some derivatives kill bacteria; others are toxic to fungi and/or cancer cells. There are also derivatives that allow the bacteria to survive in an environment that is hostile to them, such as the human body. These virulence factors are often crucial for the bacteria to become pathogenic.
Biochemically, all phenazines are derived from simple basic structures, such as the phenazine-1,6-dicarboxylic acid or phenazine-1-carboxylic acid, whose biosynthesis is well understood. However, these initial structures can be drastically modified in the periphery so that a large number of phenazine derivatives are possible, several of which can indeed be found in different bacteria. The Molecular Biotechnology research group led by Professor Helge Bode has now succeeded in identifying new mechanisms that allow the bacteria to modify these simple basic structures, resulting in derivatives that act on both Gram-positive and Gram-negative bacteria, as well as on cells of higher organisms.
“Bacteria are able to determine which derivatives should be created using a central new aldehyde intermediate as well as the activation of a second biosynthetic gene cluster," explains Dr. Yi-Ming Shi, who investigated this system during a Humboldt scholarship. This means that bacteria use mechanisms for drug development similar to those used in pharmaceutical research, where new derivatives are produced using the same basic structures. Most likely the bacteria use the phenazines to kill other bacteria and fungi that are food competitors in their particular ecosystem. Using a strategy of creating many different kinds of derivatives, the bacteria are well equipped to counteract unknown competitors, as the cocktail of derivatives exhibits a wide range of biological activity.
“It would now be fascinating to find out how bacteria actually recognise which derivatives are required at a given time," states Helge Bode. “Either they produce only those derivatives that are actually required, or the bacteria keep an arsenal of derivatives so that they are prepared for any situation."
The group will therefore continue their research in this area. First results on the underlying regulation mechanisms that could also be used for biotechnical applications appear promising.
Publication: Yi-Ming Shi, Alexander O. Brachmann, Margaretha Westphalen, Nick Neubacher, Nicholas J. Tobias, Helge B. Bode, Dual phenazine gene clusters enable diversification during biosynthesis. Nature Chemical Biology, 2019, 10.1038/s41589-019-0246-1.
A picture may be downloaded at: http://www.uni-frankfurt.de/76883939
Caption: Examples of the phenazine cocktail produced by Xenorhabdus szentirmaii bacteria. Phenazines are not only bioactive, but also exhibit the colours depicted here. Credit: Dr. Yi-Ming Shi
Further information: Professor Helge B. Bode, Molecular Biotechnology, Faculty 15, Riedberg Campus, Tel.: +49 69 798-29557, email@example.com.