Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Entomology, Max Planck Institute of Chemical Ecology, Jena, Germany.
J Mol Evol. 2018 Jul;86(6):379-394. doi: 10.1007/s00239-018-9854-8. Epub 2018 Jul 4.
Cyanogenic glucosides are widespread defence compounds in plants, and they are also found in some arthropods, especially within Lepidoptera. The aliphatic linamarin and lotaustralin are the most common cyanogenic glucosides in Lepidoptera, and they are biosynthesised de novo, and/or sequestered from food plants. Their biosynthetic pathway was elucidated in the burnet moth, Zygaena filipendulae, and consists of three enzymes: two cytochrome P450 enzymes, CYP405A2 and CYP332A3, and a glucosyl transferase, UGT33A1. Heliconius butterflies also produce linamarin and lotaustralin and have close homologs to CYP405A2 and CYP332A3. To unravel the evolution of the pathway in Lepidoptera, we performed phylogenetic analyses on all available CYP405 and CYP332 sequences. CYP332 sequences were present in almost all Lepidoptera, while the distribution of CYP405s among butterflies and moths was much more limited. Negative purifying selection was found in both CYP enzyme families, indicating that the biosynthesis of CNglcs is an old trait, and not a newly evolved pathway. We compared CYP405A2 to its close paralog, CYP405A3, which is not involved in the biosynthetic pathway. The only significant difference between these two enzymes is a smaller substrate binding pocket in CYP405A2, which would make the enzyme more substrate specific. We consider it likely that the biosynthetic pathway of CNglcs in butterflies and moths have evolved from a common pathway, perhaps based on a predisposition for detoxifying aldoximes by way of a CYP332. Later the aldoxime metabolising CYP405s evolved, and a UGT was recruited into the pathway to establish de novo biosynthesis of CNglcs.
氰基葡萄糖苷是植物中广泛存在的防御化合物，也存在于一些节肢动物中，尤其是鳞翅目昆虫中。脂肪族的亚麻苦苷和澳洲茄碱是鳞翅目昆虫中最常见的氰基葡萄糖苷，它们是从头合成的，和/或从食物植物中隔离出来的。它们的生物合成途径在毛茛灰蝶中得到了阐明，由三种酶组成：两种细胞色素 P450 酶 CYP405A2 和 CYP332A3，以及一种葡萄糖基转移酶 UGT33A1。凤蝶也产生亚麻苦苷和澳洲茄碱，并且与 CYP405A2 和 CYP332A3 有密切的同源物。为了解开鳞翅目昆虫中该途径的进化，我们对所有可用的 CYP405 和 CYP332 序列进行了系统发育分析。CYP332 序列几乎存在于所有鳞翅目昆虫中，而 CYP405s 在蝴蝶和蛾中的分布则更为有限。在这两种细胞色素酶家族中都发现了负净化选择，表明 CNglcs 的生物合成是一个古老的特征，而不是新进化的途径。我们将 CYP405A2 与其密切的旁系同源物 CYP405A3 进行了比较，后者不参与生物合成途径。这两种酶唯一的显著差异是 CYP405A2 的底物结合口袋较小，这使得该酶的底物特异性更强。我们认为，蝴蝶和蛾中 CNglcs 的生物合成途径可能是从一个共同的途径进化而来的，也许是基于通过 CYP332 解毒醛肟的倾向。后来，醛肟代谢的 CYP405 进化了，一个 UGT 被招募到该途径中，建立了 CNglcs 的从头生物合成。
