Keratinimicins and Keratinicyclins-
Novel families of antibacterial and antiviral agents
Researchers at Princeton University have developed a rapid genetics-free method for eliciting and detecting cryptic metabolites. Utilizing this approach, the inventors have activated production of diverse cryptic metabolites and characterized several novel families, including the keratinimicins and keratinicyclins. Keratinimicins A & B are highly bioactive against several pathogenic bacteria, while keratinicyclins B & C have antiviral properties and show 20-fold higher potency than Ribavirin against Respiratory Syncytial Virus (RSV). At inhibitory concentrations, keratinicyclins do not exhibit toxicity to human cells.
• Identification of cryptic metabolites from diverse microorganisms with desired activities
• Enhanced production of known bioactive metabolites from any source
• Keratinimicins A & B are potent antibacterials against a number of pathogenic strains
• Keratinicyclins B & C are antiviral agents with 20-fold higher potency than Ribavirin against Respiratory Syncytial Virus (RSV)
• Rapid activation and identification
• Genetics-free workflow can be used for an organism whose genome sequence is not known or is genetically intractable
The inventors are using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites that are then isolated and characterized. The key feature of this invention is that it allows for targeted activation of any silent biosynthetic pathway in diverse microorganisms.
This invention will allow for a rapid and genetics-free activation and identification of cryptic metabolites from diverse microorganisms with the desired bioactivity. The method can also be used to enhance production of known bioactive metabolites from any source. Furthermore, the keratinimicins and keratinicyclins can be further tailored, by synthetic chemistry approaches, to deliver new, semi-synthetic drug candidates and/or to enhance their pharmaceutical approaches.
Stage of Development
We have experimentally verified the method and isolated novel metabolites from diverse bacteria, which show potent bioactivities, including antibacterial and antiviral properties.
Xu F, Wu Y, Zhang C, Davis KM, Moon K, Bushin LB, Seyedsayamdost MR. A genetics-free method for high-throughput discovery of cryptic microbial metabolites. Nat Chem Biol. 2019 Feb;15(2):161-168.
Mohammad R. Seyedsayamdost is Associate Professor of Chemistry and Molecular Biology at Princeton University. His research focuses on the discovery of new, bioactive small molecules and their biosynthetic pathways form microbial sources. Presently, his lab is devising novel strategies for the characterization of drug-like natural products that have not been accessed by current or traditional methods. The Seyedsayamdost group employs a multi-disciplinary approach by combining techniques from a number of fields, including genetics, microbiology, protein biochemistry and natural products chemistry.
Fei Xu is currently a postdoctoral researcher in Dr. Seyedsayamdost’s laboratory. He obtained his Ph.D in Chemistry from Shanghai Jiao Tong University in China.
Yihan Wu is a former graduate student in Dr. Seyedsayamdost’s laboratory.
Leah Bushin is currently a graduate student in Dr. Seyedsayamdost’s laboratory.
Katherine Davis is currently a postdoctoral researcher in the Department of Chemistry. She obtained her Ph.D in Physics from Purdue University.
Intellectual Property Status
Patent protection is pending. Princeton University is currently looking for Industry collaborators to further develop and commercialize this technology.
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