Discovery of conserved peptide sequences to gain insight into cyclopeptide alkaloid formation in Ceanothus americanus

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Ethan B. Underwood (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Jonathan R. Chekan

Abstract: Cyclopeptide alkaloids are a large and abundant class of plant cyclopeptides with over 200 known analogs and a range of bioactivities. While these molecules have been known and studied for decades, their biosynthetic pathways remain a mystery. Utilizing a transcriptome-mining approach, we have linked cyclopeptide alkaloids from Ceanothus americanus to dedicated ribosomally synthesized and post-translationally modified peptide (RiPP) precursor peptides. This approach has become a way to uncover precursor peptides to search for putative cores which could lead to new cyclopeptide alkaloid compound discoveries. Our approach yielded two new putative cores which were confirmed by metabolomic, fragmentation, and transcriptome data. It has also confirmed the core sequences for the more than ten known compounds produced by C. americanus. Some of the compounds produced by C. americanus are known to have anti-plasmodial, anti-inflammatory, anti-bacterial, anti-fungal, and some sedative activity.1 C. americanus, also known as New Jersey Tea, has been used for many generations in folk medicine to treat blood coagulation, pressure, spleen pain, and even cancer.2 These results have allowed us to explore the plant for new putative cores and has set the groundwork for determination of the genes responsible for the biosynthetic pathways and bioactivity studies of the known and new compounds.

Additional Information

Publication
Thesis
Language: English
Date: 2022
Keywords
Ceanothus americanus, Cyclopeptide alkaloids, Natural Products, Plant side-chain-cross-linked cyclopeptides, RiPPs
Subjects
New Jersey tea
Amino acid sequence
Natural products

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