Scientist Prof. Dr. Yvonne Mast and her team are developing a new method for derivatizing antibiotics
Schematic illustration of the biotransformation-coupled mutasynthesis approach
Researchers around Professor Dr. Yvonne Mast, head of the Bioresources Department for Bioeconomy and Health Research at the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, have developed a new method for modifying (derivatizing) antibiotics. Antibiotics are medically important active ingredients that are often produced by microorganisms. Such natural products often have a chemically complex structure and are therefore difficult or impossible to produce chemically or to change through semi-synthesis. However, in order to improve the effectiveness of the substances or, as with antibiotics, to create resistance-breaking properties, the substances often need to be adapted. Mutasynthesis offers an alternative to chemical modification of substances, derivatization. This involves creating mutants of the microorganisms that produce an antibiotic. The genes for the antibiotic precursor(s) are inactivated so that they can no longer be produced by the microorganism itself. By “feeding” modified precursors, the precursor derivatives, to the mutants, these are then incorporated into the antibiotic precursor molecule and in this way new antibiotic derivatives are produced.
Mutasynthesis approach to modifying an antibiotic
The study by Professor Mast’s working group, recently published in an internationally renowned journal, describes a new mutasynthesis approach for the derivatization of the antibiotic pristinamycin I. Pristinamycin is a streptogramin antibiotic that doctors use as an emergency medication against resistant pathogens. “We modified pristinamycin I based on the amino acid precursor phenylglycine through mutasynthesis,” explains antibiotic researcher Yvonne Mast. “This was only possible because we identified and functionally characterized the phenylglycine biosynthesis genes in previous work. In the current work, we were able to generate two new halogenated, bioactive pristinamycin I derivatives. The novelty of the current study is due to the fact that we coupled the mutasynthesis with a biotransformation process through which the phenylglycine derivative precursor is provided by a genetically manipulated bacterial strain (E. coli strain). To date, this is the only biotechnological process described in this way, which we call mutasynthesis 2.0,” says the professor, summarizing the research results.
Originalpublikation:
Hennrich O, Weinmann L, Kulik A, Harms K, Klahn P, Youn J-W, Surup F, Mast Y (2023) Biotransformation-coupled mutasynthesis for the generation of novel pristinamycin derivatives by engineering the phenylglycine residue. RSC Chem Biol. 4:1050-1063.
doi: 10.1039/d3cb00143a.
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About the Leibniz Institute DSMZ
The Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures GmbH is the world‘s most diverse collection of biological resources (bacteria, archaea, protists, yeasts, fungi, bacteriophages, plant viruses, genomic bacterial DNA as well as human and animal cell cultures). At the DSMZ, microorganisms and cell cultures are collected, researched and archived. As an institution of the Leibniz Association, the DSMZ, with its extensive scientific services and biological resources, has been a global partner for research, science and industry since 1969. The DSMZ is recognized as a non-profit organization, the first registered collection in Europe (Regulation (EU) No. 511/2014) and certified according to the quality standard ISO 9001:2015. As a patent depository, it offers the only nationwide opportunity to deposit biological material in accordance with the requirements of the Budapest Treaty. In addition to scientific service, research is the second pillar of the DSMZ. The institute, based on the Science Campus Braunschweig-Süd, houses more than 85,000 cultures and biomaterials and has around 220 employees. www.dsmz.de
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The Leibniz Association connects 96 independent research institutions. Their focus ranges from natural, engineering and environmental sciences to economics, spatial and social sciences and the humanities. Leibniz Institutes are dedicated to socially, economically and ecologically relevant questions. They conduct knowledge- and application-oriented research, including in the overarching Leibniz research associations, are or maintain scientific infrastructures and offer research-based services. The Leibniz Association focuses on knowledge transfer, especially with the Leibniz research museums. It advises and informs politics, science, business and the public. Leibniz institutions maintain close cooperation with universities – in the form of the Leibniz Science Campi, with industry and other partners at home and abroad. They are subject to a transparent and independent assessment process. Due to their national importance, the federal and state governments jointly support the institutes of the Leibniz Association. The Leibniz Institutes employ around 20,500 people, including 11,500 scientists. The total budget of the institutes is 2 billion euros. www.leibniz-gemeinschaft.de
The DSMZ is the largest bioresource center in the world. The collection currently contains over 85,000 bioresources.
Company contact
Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures
PhDr. Sven-David Müller, M.Sc.
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38124 Braunschweig
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Press contact
Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures
Sven David Müller
Inhoffenstraße 7 B
38124 Braunschweig
0531-5312616300