Li et.al_Science_source_data

Many plant specialized metabolites function in herbivore defense and abrogating particular steps in their biosynthetic pathways frequently causes autotoxicity. However, the molecular mechanisms underlying their defense and autotoxicity remain unclear. Here, we show that silencing two cytochrome P450s involved in diterpene biosynthesis in the wild tobacco, <i>Nicotiana attenuata</i>, causes severe autotoxicity symptoms that result from the inhibition of sphingolipid biosynthesis by non-controlled hydroxylated diterpene derivatives. Moreover, the diterpene’s defensive function is achieved by inhibiting herbivore sphingolipid biosynthesis through post-ingestive backbone hydroxylation products. Thus, by regulating metabolic modifications, tobacco plants avoid autotoxicity and gain herbivore defense. The post-digestive duet that occurs between plants and their insect herbivores can reflect the plant’s solutions to the “toxic waste dump” problem of using potent chemical defenses.