Publications

Peek, J.; Bhattacharjee, A.; Burian, J.; Hsieh, D. C.-C.; Hernandez, Y.; Ternei, M.; Panfil, C.; Brady, S. F. Environmental Resistome–Guided Development of Resistance-Tolerant Antibiotics. Proceedings of the National Academy of Sciences 2025, 122 (21), e2504781122. 10.1073/pnas.2504781122.

Kan, J.; Morales-Amador, A.; Hernandez, Y.; Ternei, M. A.; Lemetre, C.; Maclntyre, L. W.; Biais, N.; Brady, S. F. Oxydifficidin, a Potent Neisseria Gonorrhoeae Antibiotic Due to DedA-Assisted Uptake and Ribosomal Protein RplL Sensitivity. eLife 2025, 13, RP99281. 10.7554/eLife.99281.

Baca, C. F.; Majumder, P.; Hickling, J. H.; Ye, L.; Teplova, M.; Brady, S. F.; Patel, D. J.; Marraffini, L. A. The CRISPR-Associated Adenosine Deaminase Cad1 Converts ATP to ITP to Provide Antiviral Immunity. Cell 2024, 187 (25), 7183-7195.e24. 10.1016/j.cell.2024.10.002.

Chen, Y.-J.; Iyer, S. V.; Hsieh, D. C.-C.; Li, B.; Elias, H. K.; Wang, T.; Li, J.; Ganbold, M.; Lien, M. C.; Peng, Y.-C.; Xie, X. P.; Jayewickreme, C. D.; van den Brink, M. R. M.; Brady, S. F.; Lim, S. K.; Parada, L. F. Gliocidin Is a Nicotinamide-Mimetic Prodrug That Targets Glioblastoma. Nature 2024, 636 (8042), 466–473. 10.1038/s41586-024-08224-z.

MacIntyre, L. W.; Koirala, B.; Rosenzweig, A.; Morales-Amador, A.; Brady, S. F. Cinnamosyn, a Cinnamoylated Synthetic-Bioinformatic Natural Product with Cytotoxic Activity. Org. Lett. 2024, 26 (21), 4433–4437. 10.1021/acs.orglett.4c00999.

Rosenzweig, A.; Spotton, K.; Bhattacharjee, A.; Morales-Amador, A.; Brady, S. F. Identification of an Optimized Clinical Development Candidate from Cilagicin, an Antibiotic That Evades Resistance by Dual Polyprenyl Phosphate Binding. ACS Infect. Dis. 2024, 10 (5), 1536–1544. 10.1021/acsinfecdis.4c00018.

Hossain, A. A.; Pigli, Y. Z.; Baca, C. F.; Heissel, S.; Thomas, A.; Libis, V. K.; Burian, J.; Chappie, J. S.; Brady, S. F.; Rice, P. A.; Marraffini, L. A. DNA Glycosylases Provide Antiviral Defence in Prokaryotes. Nature 2024, 629 (8011), 410–416. 10.1038/s41586-024-07329-9.

Banh, D. V.; Roberts, C. G.; Morales-Amador, A.; Berryhill, B. A.; Chaudhry, W.; Levin, B. R.; Brady, S. F.; Marraffini, L. A. Bacterial cGAS Senses a Viral RNA to Initiate Immunity. Nature 2023, 623 (7989), 1001–1008. 10.1038/s41586-023-06743-9.

Wang, Z.; Kasper, A.; Takahashi, M.; Morales Amador, A.; Bhattacharjee, A.; Kan, J.; Hernandez, Y.; Ternei, M.; Brady, S. F. Tapcin, an In Vivo Active Dual Topoisomerase I/II Inhibitor Discovered by Synthetic Bioinformatic Natural Product (Syn-BNP)-Coupled Metagenomics. Angewandte Chemie International Edition 2024, 63 (17), e202317187. 10.1002/anie.202317187.

Rosenzweig, A. F.; Wang, Z.; Morales-Amador, A.; Spotton, K.; Brady, S. F. A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates. ACS Infect. Dis. 2023, 9 (12), 2394–2400. 10.1021/acsinfecdis.3c00475.

Burian, J.; Libis, V. K.; Hernandez, Y. A.; Guerrero-Porras, L.; Ternei, M. A.; Brady, S. F. High-Throughput Retrieval of Target Sequences from Complex Clone Libraries Using CRISPRi. Nat Biotechnol 2022, 1–5. 10.1038/s41587-022-01531-8.

Libis, V.; MacIntyre, L. W.; Mehmood, R.; Guerrero, L.; Ternei, M. A.; Antonovsky, N.; Burian, J.; Wang, Z.; Brady, S. F. Multiplexed Mobilization and Expression of Biosynthetic Gene Clusters. Nat Commun 2022, 13 (1), 5256. 10.1038/s41467-022-32858-0.

Wang, Z.;  Koirala, B.;  Hernandez, Y.;  Zimmerman, M.;  Park, S.;  Perlin, D. S.; Brady, S. F., A naturally inspired antibiotic to target multidrug-resistant pathogens. Nature 2022, 601 (7894), 606-611. 10.1038/s41586-021-04264-x

Wang, Z.;  Koirala, B.;  Hernandez, Y.;  Zimmerman, M.; Brady, S. F., Bioinformatic prospecting and synthesis of a bifunctional lipopeptide antibiotic that evades resistance. Science 2022, 376 (6596), 991-996. 10.1126/science.abn4213

Wang, Z.;  Koirala, B.;  Hernandez, Y.; Brady, S. F., Discovery of Paenibacillaceae Family Gram-Negative-Active Cationic Lipopeptide Antibiotics Using Evolution-Guided Chemical Synthesis. Organic letters 2022, 24 (27), 4943-4948. 10.1021/acs.orglett.2c01879

Wang, Z.;  Forelli, N.;  Hernandez, Y.;  Ternei, M.; Brady, S. F., Lapcin, a potent dual topoisomerase I/II inhibitor discovered by soil metagenome guided total chemical synthesis. Nat Commun 2022, 13 (1), 842. 10.1038/s41467-022-28292-x

Peek, J.;  Koirala, B.; Brady, S. F., Synthesis and evaluation of dual-action kanglemycin-fluoroquinolone hybrid antibiotics. Bioorg Med Chem Lett 2022, 57, 128484. 10.1016/j.bmcl.2021.128484

Li, L.;  Koirala, B.;  Hernandez, Y.;  MacIntyre, L. W.;  Ternei, M. A.;  Russo, R.; Brady, S. F., Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens. Nat Microbiol 2022, 7 (1), 120-131. 10.1038/s41564-021-01013-8

Cohen, L. J.;  Han, S. M.;  Lau, P.;  Guisado, D.;  Liang, Y.;  Nakashige, T. G.;  Ali, T.;  Chiang, D.;  Rahman, A.; Brady, S. F., Unraveling function and diversity of bacterial lectins in the human microbiome. Nat Commun 2022,13 (1), 3101. 10.1038/s41467-022-29949-3

Wang, Z.;  Kasper, A.;  Mehmood, R.;  Ternei, M.;  Li, S.;  Freundlich, J. S.; Brady, S. F., Metagenome-Guided Analogue Synthesis Yields Improved Gram-Negative-Active Albicidin- and Cystobactamid-Type Antibiotics. Angewandte Chemie 2021, 60 (41), 22172-22177. 10.1002/anie.202104874

Piscotta, F. J.;  Whitfield, S. T.;  Nakashige, T. G.;  Estrela, A. B.;  Ali, T.; Brady, S. F., Multiplexed functional metagenomic analysis of the infant microbiome identifies effectors of NF-kappaB, autophagy, and cellular redox state. Cell Rep 2021, 36 (12), 109746. 10.1016/j.celrep.2021.109746

Piscotta, F. J.;  Hoffmann, H. H.;  Choi, Y. J.;  Small, G. I.;  Ashbrook, A. W.;  Koirala, B.;  Campbell, E. A.;  Darst, S. A.;  Rice, C. M.; Brady, S. F., Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals. mSphere 2021, 6 (6), e0071121. 10.1128/mSphere.00711-21

Li, L.;  Maclntyre, L. W.; Brady, S. F., Refactoring biosynthetic gene clusters for heterologous production of microbial natural products. Curr Opin Biotechnol 2021, 69, 145-152. 10.1016/j.copbio.2020.12.011

Li, L.;  MacIntyre, L. W.;  Ali, T.;  Russo, R.;  Koirala, B.;  Hernandez, Y.; Brady, S. F., Biosynthetic Interrogation of Soil Metagenomes Reveals Metamarin, an Uncommon Cyclomarin Congener with Activity against Mycobacterium tuberculosis. Journal of natural products 2021, 84 (4), 1056-1066. 10.1021/acs.jnatprod.0c01104

Sun, Z.;  Shang, Z.;  Forelli, N.;  Po, K. H. L.;  Chen, S.;  Brady, S. F.; Li, X., Total Synthesis of Malacidin A by beta-Hydroxyaspartic Acid Ligation-Mediated Cyclization and Absolute Structure Establishment. Angewandte Chemie 2020, 59 (45), 19868-19872. 10.1002/anie.202009092

Peek, J.;  Xu, J.;  Wang, H.;  Suryavanshi, S.;  Zimmerman, M.;  Russo, R.;  Park, S.;  Perlin, D. S.; Brady, S. F., A Semisynthetic Kanglemycin Shows In Vivo Efficacy against High-Burden Rifampicin Resistant Pathogens. ACS Infect Dis 2020, 6 (9), 2431-2440. 10.1021/acsinfecdis.0c00223

Dror, B.;  Wang, Z.;  Brady, S. F.;  Jurkevitch, E.; Cytryn, E., Elucidating the Diversity and Potential Function of Nonribosomal Peptide and Polyketide Biosynthetic Gene Clusters in the Root Microbiome. mSystems 2020, 5(6). 10.1128/mSystems.00866-20

Chu, J.;  Koirala, B.;  Forelli, N.;  Vila-Farres, X.;  Ternei, M. A.;  Ali, T.;  Colosimo, D. A.; Brady, S. F., Synthetic-Bioinformatic Natural Product Antibiotics with Diverse Modes of Action. Journal of the American Chemical Society 2020, 142 (33), 14158-14168. 10.1021/jacs.0c04376