Extended Data Fig. 1: The rationale of resistance-gene-directed discovery of a natural herbicide with a new mode of action.

a, Phylogenetic tree of DHAD among bacteria, fungi and plants. The evolutionary history was inferred by using the neighbour-joining method (MEGA7). Scale-bar units represent the number of amino acid substitutions per site. b, Representatives of small molecules that inhibit DHAD in vitro, but fail to inhibit plant growth. c, Examples of co-localization of biosynthetic gene clusters (BGCs) and targets. The biosynthetic core genes are shown in blue and the self-resistance enzymes (SREs) are shown in red. The blockbuster cholesterol-lowering lovastatin drug targets HMG-CoA reductase (HMGR) in eukaryotes. In the fungus A. terreus that produces lovastatin, a second copy of HMGR encoded by ORF8 is present in the gene cluster (top). The BGC of the immunosuppressant mycophenolic acid from Penicillium sp. contains a second copy of inosine monophosphate dehydrogenase (IMPDH), which represents the SRE to this cluster (bottom).