A first-in-class dimethyl 2-acetamido terephthalate inhibitor targeting Conyza canadensis SHMT1 with a novel herbicidal mode-of-action

•The Conyza Canadensis SHMT1 (CcSHMT1) structure was firstly resolved and a typical α-class PLP-dependent enzyme.•The dimethyl 2-acetamido terephthalate containing compounds had excellent herbicidal activity through virtual screening and biological assays.•The compound 9ay (IC 50 =193.8 g a.i./ha) exhibited the highest herbicidal efficiency and had no obvious side-effect on maize.•The first-in-class CcSHMT1 inhibitor that could be developed as a potent herbicide with a new mode-of-action.