The rhizosphere microbiome is a diverse microbiome that is sustained by an equilibrium of both mutualistic and parasitic relationships of its inhabitant microorganisms. This coexistence entices the study of small molecules produced in such environments and how they facilitate survival. Our interest lies in promysalin, a small molecule isolated from the rhizosphere in 2011. Promysalin is a potent species-specific inhibitor of Gram-negative pathogen, Pseudomonas aeruginosa. Our work began with determining the natural stereochemistry via synthesis and biological assays which lead to a DTS guided analog library, and has recently culminated in target identification.
Giglio, K.; Keohane, C.E.; Stodghill, P.; Steele, A.D.; Fetzer, C.; Sieber, S.A.; Filiatrault, M.J.*; Wuest, W.M.* ” Transcriptomic profiling suggest that Promysalin alters metabolic flux, motility, and iron regulation in Pseudomonas putida KT2440″ ACS Infectious Diseases 2018 4, 1179. DOI: 10.1021/acsinfecdis.8b00041
Keohane, C.E.; Steele, A.D.; Fetzer, C.; Khowsathit, J.; Van Tyne, D.; Moynie, L.; Gilmore, M.S.; Karanicolas, J.; Sieber, S.A.; Wuest, W.M.* “Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase” J. Am. Chem. Soc. 2018 140(5),1774-1782. DOI: 10.1021/jacs.7b11212
Steele, A.D.; Keohane, C.E.; Knouse, K.W.; Rossiter, S.E.; Williams, S.J.; Wuest, W.M.* “Diverted Total Synthesis of Promysalin Analogs Demonstrates that an Iron-Binding Motif is Responsible for its Narrow-spectrum Antibacterial Activity” J. Am. Chem. Soc. 2016 138, 5833. DOI: 10.1021/jacs.6b03373
Steele, A.D.; Knouse, K.W.; Keohane, C.E.; Wuest, W.M.* “Total Synthesis and Biological Evaluation of (-)-Promysalin” J. Am. Chem. Soc. 2015 137, 7314. DOI: 10.1021/jacs.5b04767