Discovery of New Cyclic Lipodepsipeptide Orfamide N via Partnership with Middle School Students from the Boys and Girls Club
We established a university-community partnership with the Boys and Girls Clubs of Chicago (BGCC)-named <i>Chicago Antibiotic Discovery La</i>b-to involve middle school students in antibiotic discovery research. In the course of working with a cohort of students from the BGCC, one student isolated a <i>Pseudomonas idahonensis</i> bacterium from a goose feces sample that produced a new cyclic lipodepsipeptide, which was characterized as orfamide N. Orfamide N is composed of ten mixed D/L-amino acids and a (<i>Z</i>)-3<i>R</i>-hydroxyhexadec-9-enoic acid residue. The planar structure of orfamide N was elucidated by one-dimensional (1D) and two-dimensional nuclear magnetic resonance (2D NMR), electrospray ionization-mass spectrometry (ESI-MS), and ozone-induced dissociation mass spectrometry (OzID-MS). The absolute configuration was determined by advanced Marfey's analysis, phylogenetic analysis of C-domains within the orfamide N biosynthetic gene cluster, and chiral high-performance liquid chromatography (HPLC) analysis of the hydrolyzed and reduced lipid tail. Orfamide N was cytotoxic against human melanoma and human ovarian cancer cells with IC<sub>50</sub> values of 11.06 and 10.50 μM, respectively. Overall, we demonstrated it is possible to integrate educational outreach with high-end natural product discovery while strengthening the relationship between the university and the community it serves.
Authors
- Mario Augustinović (ORCID: https://orcid.org/0000-0003-2120-8145)
- Alessandra S. Eustáquio (ORCID: https://orcid.org/0000-0002-7852-7844)
- Xabier Bilbao Lopez
- Manead Khin (ORCID: https://orcid.org/0000-0002-5744-9584)
- Nyssa K. Krull
- Qibin Zhang (ORCID: https://orcid.org/0000-0002-6135-8706)
- Vitor B. Lourenzon (ORCID: https://orcid.org/0000-0002-5947-4919)
- Scott G. Franzblau (ORCID: https://orcid.org/0000-0002-8698-0243)
- Mallique Qader (ORCID: https://orcid.org/0000-0003-0817-3435)
- Nguyen Duc Dat (ORCID: https://orcid.org/0009-0003-3803-306X)
- Brian T. Murphy (ORCID: https://orcid.org/0000-0002-1372-3887)
- Joanna E. Burdette (ORCID: https://orcid.org/0000-0002-7271-6847)
- Ashraf M. Omar
- A. G. Nugent
- Enock Mpofu (ORCID: https://orcid.org/0000-0001-8847-3109)
- Gauri Shetye (ORCID: https://orcid.org/0000-0001-6282-2833)
- Sang‐Hyun Cho (ORCID: https://orcid.org/0000-0003-0926-6246)
- Jonathon Rodriguez (ORCID: https://orcid.org/0000-0003-2712-3791)
- Jie Tan
- Camarria Williams
Institutions
- Massachusetts College of Pharmacy and Health Sciences (US)
- University of North Carolina at Greensboro (US)
- University of Illinois Chicago (US)
- Boys & Girls Clubs of America (US)
- Center for Translational Molecular Medicine (NL)
Publication Details
- Journal
- ACS Omega
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1021/acsomega.4c07459
- Citations
- 3
- Primary Topic
- Beetle Biology and Toxicology Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.86
Funders
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- Illinois-Indiana Sea Grant, University of Illinois
- University of Illinois at Chicago
- University of North Carolina at Greensboro
- National Institute of Diabetes and Digestive and Kidney Diseases