Serine hydroxymethyl transferase is a binding target of caprylic acid: Uncovering a novel molecular target for a herbicide and for producing caprylic acid-tolerant crops

Abstract Identification of new binding targets is essential for the development of herbicides and phytotoxin-tolerant crops. Caprylic acid (CAP) is a safe and non-selective bio-herbicide in uncultivated areas. However, the herbicidal action of CAP remains unclear. Herein, metabolomic and proteomic profiling indicated that a serine hydroxymethyl transferase in Conyza canadensis ( Cc SHMT1) is a promising candidate binding targeted for CAP. The protein abundance and activity of Cc SHMT1 were decreased in a time- and dosage-dependent manners after CAP treatment. CAP competes with phenyl-serine at the binding sites, decreasing the enzymatic activity of Cc SHMT1. Overexpression of CcSHMT1, AtSHMT1 and OsSHMT1 in Arabidopsis or rice endowed plants with high tolerance to CAP treatment, whereas the knockout of osshmt1 led to death of plants under normal atmospheric conditions. Furthermore, T194A, T194A/ M195V and D209N Osshmt1 mutant plants derived from base editing exhibited tolerance to CAP. CAP bound to Cc SHMT1 with high affinity, and Ala191 in the key domains of N-terminus was identified to be critical for the binding site of CAP. Collectively, our findings demonstrate that Cc SHMT1 is a binding target for herbicidal activity of CAP. This study marks a key step in the druggability of SHMT inhibitors and represents an attractive target for phytotoxin-tolerant crops.