Triterpenes are one of the most diverse groups of plant natural products, with important roles in plant defense and wide use in medicine, food, and cosmetics. So far, studies on triterpene biosynthesis have largely focused on eudicot plants, while little is known about triterpene biosynthesis in monocots. Here, we set out to expand current knowledge of triterpene chemistry and biochemistry in monocots and to investigate mechanisms of metabolic diversification in this group of plants, and specifically in the cereals group, which together provides more than half of the global human caloric intake. A genome-wide search of pathogen-induced biosynthetic gene clusters (BGCs) in wheat and Brachypodium distachyon ultimately led us to discover two triterpenoids, namely ellarinacin and brachynacin, characterize their biosynthetic pathways and obtain data supporting their putative roles in defense against plant pathogens. We also expanded our investigations beyond the initially planned focus on triterpenes, and further discovered novel metabolic pathways in wheat, which produce defense-related flavonoids and diterpenes. The flavonoid-, diterpene- and triterpene-associated BGCs we identified in wheat were also found to be regulated by a highly overlapping network of transcription factors predicted to interact with multiple genes from the pathogen-responsive BGCs identified. These findings advance our understanding of chemical defenses in wheat and open up new avenues for enhancing disease resistance in this agriculturally important crop. They also exemplify the power of transcriptional networks to discover the biosynthesis of chemical defenses in plants with large, complex genomes.
