Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in the shikimate pathway of Enterococcus faecalis Cheung, Vivian W.N. Xue, Bo Hernandez-Valladares, Maria Go, Maybelle K. Tung, Alvin Aguda, Adeleke H. Robinson, Robert C. Yew, Wen S. This research was supported by grants from the Ministry of Education, the National Medical Research Council and the National Research Foundation of Singapore to W.S.Y, and grants from the Biomedical Research Council of A*STAR to R.C.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Due to the emergence of resistance toward current antibiotics, there is a pressing need to develop the next generation of antibiotics as therapeutics against infectious and opportunistic diseases of microbial origins. The shikimate pathway is exclusive to microbes, plants and fungi, and hence is an attractive and logical target for development of antimicrobial therapeutics. The Gram-positive commensal microbe, Enterococcus faecalis, is a major human pathogen associated with nosocomial infections and resistance to vancomycin, the "drug of last resort". Here, we report the identification of several polyketide-based inhibitors against the E. faecalis shikimate pathway enzyme, 3-dehydroquinate dehydratase (DHQase). In particular, marein, a flavonoid polyketide, both inhibited DHQase and retarded the growth of Enterococcus faecalis. The purification, crystallization and structural resolution of recombinant DHQase from E. faecalis (at 2.2 Å resolution) are also reported. This study provides a route in the development of polyketide-based antimicrobial inhibitors targeting the shikimate pathway of the human pathogen E. faecalis. 2026-01-15T13:08:13Z 2026-01-15T13:08:13Z 2014-07-29 journal article Cheung VWN, Xue B, Hernandez-Valladares M, Go MK, Tung A, et al. (2014) Identification of Polyketide Inhibitors Targeting 3-Dehydroquinate Dehydratase in the Shikimate Pathway of Enterococcus faecalis. PLoS ONE 9(7): e103598. doi:10.1371/journal.pone.0103598 https://hdl.handle.net/10481/109761 10.1371/journal.pone.0103598 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Plos One