Leading PI: Rolf Müller (HIPS)
Escherichia coli, designed to be generally regarded as safe (GRAS) (e.g., ClearColi, E. coli Nissle), will be genetically engineered to produce antibiotics on demand. This project involves developing inducible production systems in collaboration with consortium partners. The focus is on two novel antibiotic classes, Darobactin and Odilorhabdin, which do not show cross-resistance with existing human antibiotics and are effective against carbapenem and colistin-resistant bacteria. These antibiotics are produced by insect-pathogenic bacteria (Xenorhabdus/Photorhabdus), closely related to E. coli, making them suitable for heterologous expression. The project leverages expertise in antibiotic biosynthesis and genetic engineering to achieve this goal.
Related Publictions:
Dey S, Seyfert CE, Fink-Straube C, Kany AM, Müller R, Sankaran S. Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic. J Biol Eng. 2024 Nov 12;18(1):66. doi: 10.1186/s13036-024-00463-y. PMID: 39533331; PMCID: PMC11559228
Präve L, Seyfert CE, Bozhüyük KAJ, Racine E, Müller R, Bode HB. Investigation of the Odilorhabdin Biosynthetic Gene Cluster Using NRPS Engineering. Angew Chem Int Ed Engl. 2024 Aug 12;63(33):e202406389. doi: 10.1002/anie.202406389. Epub 2024 Jul 10. PMID: 38801753.
Seyfert CE, Müller AV, Walsh DJ, Birkelbach J, Kany AM, Porten C, Yuan B, Krug D, Herrmann J, Marlovits TC, Hirsch AKH, Müller R. New Genetically Engineered Derivatives of Antibacterial Darobactins Underpin Their Potential for Antibiotic Development. J Med Chem. 2023 Dec 14;66(23):16330-16341. doi: 10.1021/acs.jmedchem.3c01660. Epub 2023 Nov 21. PMID: 38093695; PMCID: PMC10726357.
C. E. Seyfert, C. Porten and R. Müller*: Darobactin – ein neues Antibiotikum in Entwicklung BIOspektrum 2023, 05, 539.
Seyfert CE, Porten C, Yuan B, Deckarm S, Panter F, Bader CD, Coetzee J, Deschner F, Tehrani KHME, Higgins PG, Seifert H, Marlovits TC, Herrmann J, Müller R. Darobactins Exhibiting Superior Antibiotic Activity by Cryo-EM Structure Guided Biosynthetic Engineering. Angew Chem Int Ed Engl. 2023 Jan 9;62(2):e202214094. doi: 10.1002/anie.202214094. Epub 2022 Dec 7. PMID: 36308277; PMCID: PMC10107326.
Groß S, Panter F, Pogorevc D, Seyfert CE, Deckarm S, Bader CD, Herrmann J, Müller R. Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering. Chem Sci. 2021 Aug 12;12(35):11882-11893. doi: 10.1039/d1sc02725e. PMID: 34659729; PMCID: PMC8442675.
