Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products categorized by their unique threaded rotaxane structure. Genome mining studies from my group and others have revealed that these peptides are found in a wide variety of different prokaryotic organisms in environments as varied as the human gut and the deep sea. This proposal will leverage the latest generation of our genome mining software to catalog all known lasso peptides in sequenced genomes. We will continuously update this list and make it available to the natural products community. Leveraging our unique insights into lasso peptide activity, we will prioritize several peptides for further structural and functional studies. In particular, we plan to study lasso peptides predicted to have novel antimicrobial activities against pathogens. Finally, we will also leverage our genome mining work to carry out an in depth biochemical and structural study of lasso peptide biosynthesis.
PROJECT RELEVANCE The proposed project focuses on the prediction and isolation of novel lasso peptides, a class of bioactive natural product. The project has a specific focus on identifying and producing lasso peptides with antimicrobial activity. This research will contribute to the arsenal of antibiotics available to treat infectious disease.
| Elashal, Hader E; Cohen, Ryan D; Elashal, Heidi E et al. (2018) Cyclic and Lasso Peptides: Sequence Determination, Topology Analysis, and Rotaxane Formation. Angew Chem Int Ed Engl 57:6150-6154 |
| Zong, Chuhan; Cheung-Lee, Wai Ling; Elashal, Hader E et al. (2018) Albusnodin: an acetylated lasso peptide from Streptomyces albus. Chem Commun (Camb) 54:1339-1342 |
| Zong, Chuhan; Wu, Michelle J; Qin, Jason Z et al. (2017) Lasso Peptide Benenodin-1 Is a Thermally Actuated [1]Rotaxane Switch. J Am Chem Soc 139:10403-10409 |
| Chekan, Jonathan R; Koos, Joseph D; Zong, Chuhan et al. (2016) Structure of the Lasso Peptide Isopeptidase Identifies a Topology for Processing Threaded Substrates. J Am Chem Soc 138:16452-16458 |
| Cheung, Wai Ling; Chen, Maria Y; Maksimov, Mikhail O et al. (2016) Lasso Peptide Biosynthetic Protein LarB1 Binds Both Leader and Core Peptide Regions of the Precursor Protein LarA. ACS Cent Sci 2:702-709 |
| Allen, Caitlin D; Chen, Maria Y; Trick, Alexander Y et al. (2016) Thermal Unthreading of the Lasso Peptides Astexin-2 and Astexin-3. ACS Chem Biol 11:3043-3051 |
| Zong, Chuhan; Maksimov, Mikhail O; Link, A James (2016) Construction of Lasso Peptide Fusion Proteins. ACS Chem Biol 11:61-8 |
| Allen, Caitlin D; Link, A James (2016) Self-Assembly of Catenanes from Lasso Peptides. J Am Chem Soc 138:14214-14217 |
| Link, A James (2015) Biosynthesis: Leading the way to RiPPs. Nat Chem Biol 11:551-2 |
| Maksimov, Mikhail O; Koos, Joseph D; Zong, Chuhan et al. (2015) Elucidating the Specificity Determinants of the AtxE2 Lasso Peptide Isopeptidase. J Biol Chem 290:30806-12 |
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