Publications

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Mohamed, O. G., A. A. Salim, Z. G. Khalil, A. H. Elbanna, P. V. Bernhardt, and R. J. Capon, "Chrysosporazines F–M: P-Glycoprotein Inhibitory Phenylpropanoid Piperazines from an Australian Marine Fish Derived Fungus, Chrysosporium sp. CMB-F294", Journal of Natural Products, vol. 83, issue 2: American Chemical Society and American Society of Pharmacognosy, pp. 497-504, 2020. Abstract
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Chigumba, D. N., L. S. Mydy, F. de Waal, W. Li, K. Shafiq, J. W. Wotring, O. G. Mohamed, T. Mladenovic, A. Tripathi, and J. Z. Sexton, "Discovery and biosynthesis of cyclic plant peptides via autocatalytic cyclases", Nature chemical biology, vol. 18, issue 1: Nature Publishing Group, pp. 18-28, 2022. Abstract
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Robertson, A. W., J. Sandoval, O. G. Mohamed, Y. Zhuang, E. E. Gallagher, J. Schmidt, L. Caratelli, A. Menon, P. J. Schultz, R. M. Torrez, et al., "Discovery of Surfactins as Inhibitors of MicroRNA Processing Using Cat-ELCCA", ACS Medicinal Chemistry LettersACS Medicinal Chemistry Letters, vol. 12, issue 6: American Chemical Society, pp. 878 - 886, 2021. AbstractWebsite
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Robertson, A. W., J. Sandoval, O. G. Mohamed, Y. Zhuang, E. E. Gallagher, J. Schmidt, L. Caratelli, A. Menon, P. J. Schultz, and R. M. Torrez, "Discovery of surfactins as inhibitors of microRNA processing using cat-ELCCA", ACS Medicinal Chemistry Letters, vol. 12, issue 6: American Chemical Society, pp. 878-886, 2021. Abstract
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Jiao, W. - H., P. Dewapriya, O. S. A. M. A. MOHAMED, Z. G. Khalil, A. A. Salim, H. - W. Lin, and R. J. Capon, "Divirensols: sesquiterpene dimers from the Australian termite nest-derived fungus Trichoderma virens CMB-TN16", Journal of natural products, vol. 82, issue 1: American Chemical Society and American Society of Pharmacognosy, pp. 87-95, 2018. Abstract
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Mohamed, O. G., S. Dorandish, R. Lindow, M. Steltz, I. Shoukat, M. Shoukat, H. Chehade, S. Baghdadi, M. McAlister-Raeburn, A. Kamal, et al., "Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique", Marine Drugs, vol. 19, no. 8, 2021. AbstractWebsite

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny EarthTM, we isolated over 1400 antibiotic-producing microbes, including 62 showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.

Mohamed, O. G., S. Dorandish, R. Lindow, M. Steltz, I. Shoukat, M. Shoukat, H. Chehade, S. Baghdadi, M. McAlister-Raeburn, and A. Kamal, "Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique", Marine drugs, vol. 19, issue 8: Multidisciplinary Digital Publishing Institute, pp. 424, 2021. Abstract
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Mohamed, O. G., Z. G. Khalil, A. A. Salim, H. Cui, A. Blumenthal, and R. J. Capon, "Lincolnenins A–D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis", The Journal of Organic ChemistryThe Journal of Organic Chemistry, vol. 86, issue 16: American Chemical Society, pp. 11011 - 11018, 2021. AbstractWebsite
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Mohamed, O. G., Z. G. Khalil, A. A. Salim, H. Cui, A. Blumenthal, and R. J. Capon, "Lincolnenins A–D: Isomeric bactericidal bianthracenes from Streptomyces lincolnensis", The Journal of Organic Chemistry, vol. 86, issue 16: American Chemical Society, pp. 11011-11018, 2020. Abstract
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Yancey, C. E., D. J. Smith, P. A. Den Uyl, O. G. Mohamed, F. Yu, S. A. Ruberg, J. D. Chaffin, K. D. Goodwin, A. Tripathi, and D. H. Sherman, "Metagenomic and Metatranscriptomic Insights into Population Diversity of Microcystis Blooms: Spatial and Temporal Dynamics of mcy Genotypes, Including a Partial Operon That Can Be Abundant and Expressed", Applied and environmental microbiology: American Society for Microbiology 1752 N St., NW, Washington, DC, pp. e02464-21, 2022. Abstract
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Mohamed, O. G., Z. G. Khalil, V. Santiago, and R. J. Capon, "Metarhizides A–C and metarhizosides A–B: PKS-NRPS macrolides and aromatic glycosides from an Australian fish gut-derived fungus, Metarhizium sp. CMB-F624", Tetrahedron, vol. 113: Pergamon, pp. 132759, 2022. Abstract
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Mohamed, O. G., Z. G. Khalil, and R. J. Capon, "N-Amino-l-Proline Methyl Ester from an Australian Fish Gut-Derived Fungus: Challenging the Distinction between Natural Product and Artifact", Marine Drugs, vol. 19, no. 3, 2021. AbstractWebsite

Further investigation into a fish gut-derived fungus Evlachovaea sp. CMB-F563, previously reported to produce the unprecedented Schiff base prolinimines A–B (1–2), revealed a new cryptic natural product, N-amino-l-proline methyl ester (5)—only the second reported natural occurrence of an N-amino-proline, and the first from a microbial source. To enable these investigations, we developed a highly sensitive analytical derivitization methodology, using 2,4-dinitrobenzaldehyde (2,4-DNB) to cause a rapid in situ transformation of 5 to the Schiff base 9, with the latter more readily detectable by UHPLC-DAD (400 nm) and HPLC-MS analyses. Moreover, we demonstrate that during cultivation 5 is retained in fungal mycelia, and it is only when solvent extraction disrupts mycelia that 5 is released to come in contact with the furans 7–8 (which are themselves produced by thermal transformation of carbohydrates during media autoclaving prior to fungal inoculation). Significantly, on contact, 5 undergoes a spontaneous condensation with 7–8 to yield the Schiff base prolinimines 1–2, respectively. Observations made during this study prompted us to reflect on what it is to be a natural product (i.e., 5), versus an artifact (i.e., 1–2), versus a media component (i.e., 7–8).

Mohamed, O. G., Z. G. Khalil, and R. J. Capon, "N-Amino-l-Proline Methyl Ester from an Australian Fish Gut-Derived Fungus: Challenging the Distinction between Natural Product and Artifact", Marine drugs, vol. 19, issue 3: Multidisciplinary Digital Publishing Institute, pp. 151, 2021. Abstract
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Mohamed, O. G., Z. G. Khalil, and R. J. Capon, "Prolinimines: N-Amino-l-Pro-methyl Ester (Hydrazine) Schiff Bases from a Fish Gastrointestinal Tract-Derived Fungus, Trichoderma sp. CMB-F563", organic letters, vol. 20, issue 2, pp. 377-380, 2018.
Mohamed, O. G., Z. G. Khalil, and R. J. Capon, "Prolinimines: N-Amino-L-Pro-methyl ester (hydrazine) Schiff bases from a fish gastrointestinal tract-derived fungus, Trichoderma sp. CMB-F563", Organic letters, vol. 20, issue 2: American Chemical Society, pp. 377-380, 2018. Abstract
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