Yeast Synthesis and Herbicidal Activity Evaluation of Aspterric Acid

Aspterric acid (AA) is a novel natural product herbicide that targets dihydroxyacid dehydratase in plants. In this study, we introduced two distinct AA biosynthesis-related gene clusters into <i>Saccharomyces cerevisiae</i> and screened the core biosynthetic enzyme, sesquiterpene cyclase, from various fungi. The combination of sesquiterpene cyclase from <i>Aspergillus taichungensis</i> IBT 19404 and two cytochrome P450s from <i>Penicillium brasilianum</i> resulted in the optimal AA synthesis efficiency in yeast, with the highest titer of 33.21 mg/L achieved by optimizing fermentation conditions in shake flasks. Moreover, the herbicidal effects of AA on weed germination and growth were evaluated. Notably, AA strongly inhibited the germination of <i>Amaranthus tricolor</i>, <i>Portulaca oleracea</i>, <i>Bidens pilosa</i>, <i>Lolium perenne</i>, and <i>Leptochloa chinensis</i>. Furthermore, AA could also inhibit the shoot and root growth of weeds with a superior inhibitory effect on roots relative to shoots. Our work not only provides a sustainable method for the biosynthesis of AA in yeast but also paves the way for the application of AA as a preemergence herbicide.