Inverted stereocontrol of iridoid synthase in snapdragon.
Inverted stereocontrol of iridoid synthase in snapdragon.
复制标题
DOI：
10.1074/jbc.m117.800979
复制
发表时间：
2017-09-01
期刊：
影响因子：
--
通讯作者：
O'Connor SE
中科院分区：
文献类型：
--
作者：
Kries H;Kellner F;Kamileen MO;O'Connor SE
环烯醚萜类天然产物存在于各种开花植物中，具有惊人的化学复杂性。在药用植物长春花中发现的环烯醚萜生物合成基因为这类天然产物的生物合成起源提供了深入的了解。然而，并不是所有的环烯醚萜都具有与长春花环烯醚萜完全相同的5 - 6双环骨架。例如，观赏花金鱼草（金鱼草，车前草科）中的环烯醚萜衍生自该支架的C7差向异构体。在这里，我们已经克隆和表征环烯醚萜合成酶从A。majus（AmISY），该酶负责在两步还原-环化序列中将8-氧代香叶醛转化为双环环烯醚萜骨架。反应产物的手性分析表明，AmISY减少C7产生相反的立体构型相比，长春花同系物CrISY。因此，AmISY的催化活性解释了金鱼草属和相关属中7-表环烯醚萜类化合物的生物合成。然而，尽管AmISY催化的还原步骤的立体选择性是清楚的，但在AmISY和CrISY中，环化步骤产生非对映异构体混合物。虽然8-氧代锗醛的还原明显是酶催化的，但环化步骤似乎受到不太严格的酶控制。
The natural product class of iridoids, found in various species of flowering plants, harbors astonishing chemical complexity. The discovery of iridoid biosynthetic genes in the medicinal plant Catharanthus roseus has provided insight into the biosynthetic origins of this class of natural product. However, not all iridoids share the exact five- to six-bicyclic ring scaffold of the Catharanthus iridoids. For instance, iridoids in the ornamental flower snapdragon (Antirrhinum majus, Plantaginaceae family) are derived from the C7 epimer of this scaffold. Here we have cloned and characterized the iridoid synthase enzyme from A. majus (AmISY), the enzyme that is responsible for converting 8-oxogeranial into the bicyclic iridoid scaffold in a two-step reduction–cyclization sequence. Chiral analysis of the reaction products reveals that AmISY reduces C7 to generate the opposite stereoconfiguration in comparison with the Catharanthus homologue CrISY. The catalytic activity of AmISY thus explains the biosynthesis of 7-epi-iridoids in Antirrhinum and related genera. However, although the stereoselectivity of the reduction step catalyzed by AmISY is clear, in both AmISY and CrISY, the cyclization step produces a diastereomeric mixture. Although the reduction of 8-oxogeranial is clearly enzymatically catalyzed, the cyclization step appears to be subject to less stringent enzyme control.