The XMAS-III

Natural halogenated compounds (NHCs) are biosynthesized by microbes as secondary metabolites. There is great interest in NHCs driven to meet processing biomedical requirements for new drugs, however, the majority of NHCs remain unidentified. To address this knowledge gap, we developed an untargeted screening method (DIPIC-Frag) to identify NHCs, and more than 2000 brominated compounds and 4000 iodinated compounds were identified in sediments. Determination of field-collected microbes confirmed the presence and biosynthesis of these compounds in marine bacteria, algal and sponge. Metagenomics and chemical profile of NHCs were further determined in freshwater and marine sediments, and chemical profiles of NHCs were found to be significantly correlated with bacteria community shift in corresponding sediments. The first interactive bacteria specie and NHCs database was thus established, building the bridge linkage between NHCs and biosynthesis bacteria species. To further characterize the biological function of these NHCs. Using 6-OH-BDE-47 as a case study, we developed a chemical proteomics method (TILS) for proteome-wide determination of protein targets. FabI was identified as the protein target by TILS, which was further validated by affinity pull-down and in vitro enzymatic assays. Overexpression of FabI rescued the growth inhibition of Escherichia coli by 6-OH-BDE-47, validating it as the primary in vivo target of 6-OH-BDE-47. Here we developed a series of methods for unbiased identification of NHCs and their protein targets, further application of these assays to identify their biosynthetic pathways in microbes will be of great interest.

Program