Naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs reveals the biosynthetic pathway of plant acetophenones
Zhai, R (Zhai, Rui) [1] ; Zhang, HJ (Zhang, Hongjuan) [1] ; Xie, YP (Xie, Yinpeng) [1] , [2] ; Zhang, SC (Zhang, Shichao) [1] ; Zhou, FL (Zhou, Fengli) [1] ; Du, X (Du, Xuan) [3] ; Chen, WF (Chen, Weifeng) [4] ; Yan, YF (Yan, Yanfang) [1] , [2] ; Zhang, J (Zhang, Jing) [1] ; Li, PM (Li, Pengmin) [1] , [2] ; Atkinson, R (Atkinson, Ross) [5] ; Wang, ZG (Wang, Zhigang) [1] ; Yang, CQ (Yang, Chengquan) [1] ; Guan, QM (Guan, Qingmei) [1] , [2] ; Ma, FW (Ma, Fengwang) [1] , [2] ; Xu, LF (Xu, Lingfei) [1] , [2]
NATURE PLANTS
DOI：10.1038/s41477-025-02082-x
Abstract
Acetophenones, which show scattered distribution across phylogenetically distant plants and fungi, play diverse roles in plant-plant, plant-insect, plant-microbiome and even animal-insect interactions. However, the enzymatic basis of acetophenone biosynthesis in plants remains unknown. Here we elucidate the complete biosynthetic pathway of picein (4-hydroxyacetophenone glucoside) from 4-coumaroyl-CoA using pear (Pyrus) as a study system. We demonstrate that in certain pear cultivars, the acetophenone moiety originates from an impaired side-chain shortening reaction of an aromatic 3-ketoacyl-CoA intermediate, a key step in the beta-oxidative biosynthesis of benzoic acid. This impairment results from a loss-of-function mutation in a peroxisomal 3-ketoacyl-CoA thiolase. The accumulated aromatic 3-ketoacyl-CoA is subsequently hydrolysed by a thioesterase and undergoes spontaneous decarboxylation to yield the acetophenone moiety. This rare metabolic phenomenon highlights that not only neofunctionalization but also loss-of-function mutations can drive diversification in plant secondary metabolism. Forward genetic approaches are powerful to shed light on such 'hidden' or recessive pathways in plants.