Nav: Home

Construction kit for custom-designed products

June 12, 2019

Many important natural products such as antibiotics, immunosuppressants, or anti-cancer drugs are produced by microorganisms. These natural products are often small peptides, which in several cases are too complex for a chemical synthesis in the laboratory. In the microbial producers of these drugs, the drugs are generated with the help of the NRPS enzymes in a manner similar to a modern automobile factory: at each station, additional parts are added to the basic structure until finally a complete automobile leaves the factory. In the case of NRPS, a specific amino acid is incorporated and processed at each station (module) so that in the end, peptides emerge that can be linear, cyclic or otherwise modified, and which can also carry unusual amino acids.

Although the basic principles of NRPS have been known for a long time, it was previously hardly possible to modify these enzymes in an easy and efficient way that also allows the complete assembly of fully artificial enzymes leading to new-to-nature peptides. While in the past NRPS modification usually led to a dramatic drop in the production titre of the desired modified peptides, the Molecular Biotechnology research group of Professor Helge Bode already published a new method in 2018 that avoided this drawback. The group has now further optimized this method allowing the easy production of new peptides in excellent yield.

"We use fragments of natural NRPS systems from different bacteria as building blocks that we connect to each other using specific assembly points we have identified," Andreas Tietze and Janik Kranz explain the research approach they developed as part of a larger team in the Bode group. "The yields are comparable to the natural production of the non-modified natural products and the new methods also enable the simple production of peptide libraries, which was not possible before".

The method is so well established, beginners can use it to produce new peptides after a short training period. But to get to this point was a long way. "Following the first promising experiments by Kenan, my PhD student at the time, we worked for a long time on the project with a major part of my group until we were certain that our method fulfilled the requirements of a robust and easily reproducible engineering method," Bode states. "Thanks to the LOEWE priority programmes MegaSyn and Translational Biodiversity Genomics, we had the necessary personnel and financial support, and could concentrate completely on the project."

The next step is to modify the first clinically relevant drugs with this method and produce them in microorganisms applying biotechnology methods. The conditions for this are good - Bode was only recently awarded one of the renowned ERC Advanced Grants from the European Research Council in order to further optimize the methods over the next five years.
-end-
Publication:

Kenan A. J. Bozhüyük, Annabell Linck, Andreas Tietze, Janik Kranz, Frank Wesche, Sarah Nowak, Florian Fleischhacker, Yan-Ni Shi, Peter Grün, Helge B. Bode: Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains, Nature Chemistry, https://www.nature.com/articles/s41557-019-0276-z; DOI: https://doi.org/10.1038/s41557-019-0276-z

An image can be downloaded here: http://www.uni-frankfurt.de/78678421

Caption: From left to right: Dr. Yan-Ni Shi, Prof. Helge Bode, Janik Kranz, Peter Grün und Andreas Tietze. Credit: Jürgen Lecher, Goethe-Universität.

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.

Current news about science, teaching, and society can be found on GOETHE-UNI online (http://www.aktuelles.uni-frankfurt.de)

Goethe University is a research-oriented university in the European financial centre Frankfurt am Main. The university was founded in 1914 through private funding, primarily from Jewish sponsors, and has since produced pioneering achievements in the areas of social sciences, sociology and economics, medicine, quantum physics, brain research, and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a "foundation university". Today, it is one of the three largest universities in Germany. Together with the Technical University of Darmstadt and the University of Mainz, it is a partner in the inter-state strategic Rhine-Main University Alliance. Internet: http://www.uni-frankfurt.de

Publisher: The President of Goethe University Editor: Dr. Anne Hardy, Science Editor, PR & Communication Department, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: -49 (0) 69 798-13035, Fax: +49 (0) 69 798-763 12531, hardy@pvw.uni-frankfurt.de

Goethe University Frankfurt

Related Peptides Articles:

Pigments by design
Researchers have discovered how to tune the optical and electrical properties of a synthetic polymer similar to melanin, a natural pigment that's the primary factor affecting skin color.
Frog slime kills flu virus
Frogs' skins were known to secrete peptides that defend them against bacteria.
Killing flu viruses with help from a frog
Frog mucus is loaded with molecules that kill bacteria and viruses, and researchers are beginning to investigate it as a potential source for new anti-microbial drugs.
A promising strategy to increase activity in antimicrobial peptides
In an article published recently in Plos One, researchers from INRS-Institut Armand-Frappier Research Centre reported a strategy that could lead to the discovery of new cationic antimicrobial peptides (CAMPs) with greatly enhanced antimicrobial properties.
Sequencing poisonous mushrooms to potentially create medicine
A team of Michigan State University scientists has genetically sequenced two species of poisonous mushrooms, discovering that they can theoretically produce billions of compounds through one molecular assembly line.
Peptides as tags in fluorescence microscopy
Advance in biomedical imaging: The Biocenter of the University of W├╝rzburg in close collaboration with the University of Copenhagen has developed an alternative approach to fluorescent tagging of proteins.
Team finds new way to attach lipids to proteins, streamlining drug development
Protein-based drugs are used in the treatment of every kind of malady, from cancer to heart disease to rheumatoid arthritis.
Machine-learning discovery and design of membrane-active peptides for biomedicine
There are approximately 1,100 known antimicrobial peptides (AMP) with diverse sequences that can permeate microbial membranes.
Toxic peptides disrupt membrane-less organelles in neurodegenerative disease
St. Jude Children's Research Hospital scientists reveal how toxic peptides that arise due to amyotrophic lateral sclerosis and frontotemporal dementia target the integrity of membrane-less organelles and trigger disease.
Peptides vs. superbugs
Several peptides have an antibacterial effect -- but they are broken down in the human body too quickly to exert this effect.

Related Peptides Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...