The parsnip webworm, Depressaria pastinacella, is restricted to two hostplant genera containing six structurally diverse furanocoumarins. Of these, imperatorin is detoxified by a specialized cytochrome P450, CYP6AB3. A previous whole‐larva transcriptome analysis confirmed the presence of nine transcripts that belong to the CYP6AE subfamily. Here, by examining midgut‐specific gene expression patterns we determined that CYP6AE89 transcripts were highly expressed and furanocoumarin‐inducible. Computer docking and energy‐minimization of a CYP6AE89 model with all six furanocoumarins showed that 5‐methoxylated bergapten and 8‐methoxylated xanthotoxin had the smallest distances from the heme to the proton‐donor residue in the catalytic I‐helix, and that the 5,8‐dimethoxylated isopimpinellin and bergapten had the smallest energy‐minimized distance from the heme oxygen to the furan ring double bond. To evaluate this prediction, we expressed the CYP6AE89 protein in an Escherichia coli system, and used it to detect high catalytic activity against the two mono‐methoxylated linear furanocoumarins – bergapten and xanthotoxin – and weak activity against isopimpinellin. Thus, CYP6AE89, like CYP6AB3, is probably specialized for detoxifying only a subset of hostplant furanocoumarins. A maximum‐likelihood tree built with six representative lepidopterans with manually annotated cytochrome P450s shows that CYP6AE89 may have evolved much faster than the other CYP6AE proteins, possibly indicative of host selection pressure.

中文翻译：

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底物特异性的细胞色素P450介导的排毒作为专门针对含呋喃香豆素的宿主植物：欧洲防风草蠕虫中的CYP6AE89的进化策略。

防风草蠕虫，Depressaria pastinacella限于两个寄主植物属，其包含六个结构不同的呋喃香豆素。其中，欧前胡素被专门的细胞色素P450 CYP6AB3解毒。先前的全幼虫转录组分析证实存在9个属于CYP6AE亚家族的转录本。在这里，通过检查中肠特异性基因表达模式，我们确定CYP6AE89转录本高表达且可被呋喃香豆素诱导。CYP6AE89模型与所有六种呋喃香豆素的计算机对接和能量最小化表明，5-甲氧基化的Bergapten和8-甲氧基化的黄酮毒素在血红素与催化I型螺旋中的质子给体残基之间的距离最小，并且5，从血红素氧到呋喃环双键的8-二甲氧基化异海洛平和佛手柑具有最小的能量最小距离。大肠杆菌系统，并用于检测对两种单甲氧基化的线性呋喃香豆素（Bergapten和Xanthotoxin）的高催化活性，以及​​对异海洛平的弱活性。因此，CYP6AE89与CYP6AB3一样，可能专门用于对一部分宿主植物呋喃香豆素进行解毒。用六个具有代表性的鳞翅类动物和人工注释的细胞色素P450构建的最大似然树显示CYP6AE89的进化可能比其他CYP6AE蛋白快得多，这可能表明宿主选择压力。